Publications
2024
Green Emily I, Jaouen Etienne, Klug Dennis, Olmo Roenick Proveti, Gautier Amandine, Blandin Stéphanie, Marois Eric
A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes Journal Article
In: Genetics and Genomics, 2024.
Abstract | Links | BibTeX | Tags: Anopheles, blandin, gene drive, Lipophorin, M3i, marois, marque, Marques, Olmo, Plasmodium, Saglin
@article{Green2024,
title = {A population modification gene drive targeting both Saglin and Lipophorin disables Plasmodium transmission in Anopheles mosquitoes},
author = {Emily I Green and Etienne Jaouen and Dennis Klug and Roenick Proveti Olmo and Amandine Gautier and Stéphanie Blandin and Eric Marois},
url = {https://elifesciences.org/articles/93142},
doi = {10.7554/eLife.93142},
year = {2024},
date = {2024-01-12},
journal = {Genetics and Genomics},
abstract = {Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this antimalarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.},
keywords = {Anopheles, blandin, gene drive, Lipophorin, M3i, marois, marque, Marques, Olmo, Plasmodium, Saglin},
pubstate = {published},
tppubtype = {article}
}
Marois Eric
Using the CRISPR / Cas9 system for genome editing in Anopheles mosquitoes Online
2024, visited: 08.01.2024.
Abstract | Links | BibTeX | Tags: Anopheles, CRISPR/Cas9, Genome editing, M3i, marois, mosquitoes
@online{Marois2024,
title = {Using the CRISPR / Cas9 system for genome editing in Anopheles mosquitoes},
author = { Eric Marois},
url = {https://hal.science/hal-04380430/document},
doi = {HAL Id: hal-04380430},
year = {2024},
date = {2024-01-08},
urldate = {2024-01-08},
journal = {HAL science},
abstract = {The advent of the CRISPR / Cas9 technology permits the targeted editing of mosquito genomes, ranging from site-directed mutagenesis of genes of interest yielding knockout mutations (which arise by insertion / deletion of a few nucleotides) to site-specific insertion of exogenous DNA sequences such as fluorescence markers or even large gene drive cassettes, themselves encoding the components of the CRISPR / Cas9 system. To obtain these heritable targeted changes, genome editing requires the delivery of Cas9 protein and its guide RNA(s) to the developing germ tissue of an embryo. Different species require adaptation of this basic principle to accommodate for their specific biology. Here, we describe a technical pipeline based on delivering the CRISPR/Cas9 components in the form of injected plasmid or as transgenes, resulting in highly efficient gene editing in Anopheles malaria vector mosquitoes. We have reliably employed these methods to mutagenize > 20 different loci of interest in Anopheles coluzzii to date. },
keywords = {Anopheles, CRISPR/Cas9, Genome editing, M3i, marois, mosquitoes},
pubstate = {published},
tppubtype = {online}
}
2023
AI Kalita, E Marois, M Kozielska, FJ Weissing, E Jaouen, Möckel MM and Rühle F, F Butter, MF Basilicata, CI Keller Valsecchi
The sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes Journal Article
In: Nature, vol. 623, pp. 175–182, 2023.
Abstract | Links | BibTeX | Tags: Anopheles, M3i, marois, SOA
@article{AI2023,
title = {The sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes},
author = {Kalita AI and Marois E and Kozielska M and Weissing FJ and Jaouen E and Möckel MM and, Rühle F and Butter F and Basilicata MF and Keller Valsecchi CI},
url = {https://www.nature.com/articles/s41586-023-06641-0},
doi = {10.1038/s41586-023-06641-0.},
year = {2023},
date = {2023-09-28},
journal = {Nature},
volume = {623},
pages = {175–182},
abstract = {The Anopheles mosquito is one of thousands of species in which sex differences play a central part in their biology, as only females need a blood meal to produce eggs. Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex chromosomal genes. However, because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved1. Here we report the discovery of a previously uncharacterized gene (sex chromosome activation (SOA)) as a master regulator of DC in the malaria mosquito Anopheles gambiae. Sex-specific alternative splicing prevents functional SOA protein expression in females. The male isoform encodes a DNA-binding protein that binds the promoters of active X chromosomal genes. Expressing male SOA is sufficient to induce DC in female cells. Male mosquitoes lacking SOA or female mosquitoes ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analyses of a DC master regulator in a non-model organism elucidates the evolutionary steps that lead to the establishment of a chromosome-specific fine-tuning mechanism.},
keywords = {Anopheles, M3i, marois, SOA},
pubstate = {published},
tppubtype = {article}
}
2020
Volohonsky Gloria, Paul-Gilloteaux Perrine, Stafkova Jitka, Soichot Julien, Salamero Jean, Levashina Elena A.
Kinetics of Plasmodium midgut invasion in Anopheles mosquitoes Journal Article
In: PLoS Pathog, vol. 16, no. 9, 2020, ISSN: 1553-7374.
Abstract | Links | BibTeX | Tags: Anopheles, M3i, Malaria, marois, midgut, Plasmodium
@article{volohonsky_plasmodium_2020,
title = {Kinetics of Plasmodium midgut invasion in Anopheles mosquitoes},
author = {Gloria Volohonsky and Perrine Paul-Gilloteaux and Jitka Stafkova and Julien Soichot and Jean Salamero and Elena A. Levashina
},
editor = {Kenneth D. Vernick, Institut Pasteur, FRANCE},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008739},
doi = {10.1371/journal.ppat.1008739},
issn = {1553-7374},
year = {2020},
date = {2020-09-18},
journal = {PLoS Pathog},
volume = {16},
number = {9},
abstract = {The traversal of the mosquito midgut cells is one of the critical stages in the life cycle of malaria parasites. Motile parasite forms, called ookinetes, traverse the midgut epithelium in a dynamic process which is not fully understood. Here, we harnessed transgenic reporters to track invasion of Plasmodium parasites in African and Indian mosquito species. We found important differences in parasite dynam- ics between the two Anopheles species and demonstrated a role of the mosquito comple- ment-like system in regulation of parasite invasion of the midgut cells.},
keywords = {Anopheles, M3i, Malaria, marois, midgut, Plasmodium},
pubstate = {published},
tppubtype = {article}
}
2015
Neafsey D E, Waterhouse R M, Abai M R, Aganezov S S, Alekseyev M A, Allen J E, Amon J, Arcà B, Arensburger P, Artemov G, Assour L A, Basseri H, Berlin A, Birren B W, Blandin Stéphanie A, Brockman A I, Burkot T R, Burt A, Chan C S, Chauve C, Chiu J C, Christensen M, Costantini C, Davidson V L M, Deligianni E, Dottorini T, Dritsou V, Gabriel S B, Guelbeogo W M, Hall A B, Han M W, Hlaing T, Hughes D S T, Jenkins A M, Jiang X, Jungreis I, Kakani E G, Kamali M, Kemppainen P, Kennedy R C, Kirmitzoglou I K, Koekemoer L L, Laban N, Langridge N, Lawniczak M K N, Lirakis M, Lobo N F, Lowy E, MacCallum R M, Mao C, Maslen G, Mbogo C, McCarthy J, Michel K, Mitchell S N, Moore W, Murphy K A, Naumenko A N, Nolan Tony, Novoa E M, O’Loughlin S, Oringanje C, Oshaghi M A, Pakpour N, Papathanos P A, Peery A N, Povelones Michael, Prakash A, Price D A, Rajaraman A, Reimer L J, Rinker D C, Rokas A, Russell T L, Sagnon N F, Sharakhova M V, Shea T, Simão F A, Simard F, Slotman M A, Somboon P, Stegniy V, Struchiner C J, Thomas G W C, Tojo M, Topalis P, Tubio J M C, Unger M F, Vontas J, Walton C, Wilding C S, Willis J H, Wu Y-C, Yan G, Zdobnov E M, Zhou X, Catteruccia Flaminia, Christophides Georges K, Collins F H, Cornman R S, Crisanti Andrea, Donnelly M J, Emrich S J, Fontaine M C, Gelbart W, Hahn M W, Hansen I A, Howell P I, Kafatos Fotis C, Kellis M, Lawson D, Louis C, Luckhart S, Muskavitch M A T, Ribeiro J M, Riehle M A, Sharakhov I V, Tu Z, Zwiebel L J, Besansky N J
Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes. Journal Article
In: Science, vol. 347, no. 6217, pp. 1258522, 2015.
Abstract | Links | BibTeX | Tags: Anopheles, blandin, genomes, M3i
@article{DE2015,
title = {Highly evolvable malaria vectors: The genomes of 16 Anopheles mosquitoes.},
author = {D E Neafsey and R M Waterhouse and M R Abai and S S Aganezov and M A Alekseyev and J E Allen and J Amon and B Arcà and P Arensburger and G Artemov and L A Assour and H Basseri and A Berlin and B W Birren and Stéphanie A Blandin and A I Brockman and T R Burkot and A Burt and C S Chan and C Chauve and J C Chiu and M Christensen and C Costantini and V L M Davidson and E Deligianni and T Dottorini and V Dritsou and S B Gabriel and W M Guelbeogo and A B Hall and M W Han and T Hlaing and D S T Hughes and A M Jenkins and X Jiang and I Jungreis and E G Kakani and M Kamali and P Kemppainen and R C Kennedy and I K Kirmitzoglou and L L Koekemoer and N Laban and N Langridge and M K N Lawniczak and M Lirakis and N F Lobo and E Lowy and R M MacCallum and C Mao and G Maslen and C Mbogo and J McCarthy and K Michel and S N Mitchell and W Moore and K A Murphy and A N Naumenko and Tony Nolan and E M Novoa and S O’Loughlin and C Oringanje and M A Oshaghi and N Pakpour and P A Papathanos and A N Peery and Michael Povelones and A Prakash and D A Price and A Rajaraman and L J Reimer and D C Rinker and A Rokas and T L Russell and N F Sagnon and M V Sharakhova and T Shea and F A Simão and F Simard and M A Slotman and P Somboon and V Stegniy and C J Struchiner and G W C Thomas and M Tojo and P Topalis and J M C Tubio and M F Unger and J Vontas and C Walton and C S Wilding and J H Willis and Y-C Wu and G Yan and E M Zdobnov and X Zhou and Flaminia Catteruccia and Georges K Christophides and F H Collins and R S Cornman and Andrea Crisanti and M J Donnelly and S J Emrich and M C Fontaine and W Gelbart and M W Hahn and I A Hansen and P I Howell and Fotis C Kafatos and M Kellis and D Lawson and C Louis and S Luckhart and M A T Muskavitch and J M Ribeiro and M A Riehle and I V Sharakhov and Z Tu and L J Zwiebel and N J Besansky},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25554792},
year = {2015},
date = {2015-01-02},
journal = {Science},
volume = {347},
number = {6217},
pages = {1258522},
abstract = {Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.},
keywords = {Anopheles, blandin, genomes, M3i},
pubstate = {published},
tppubtype = {article}
}
2009
Fraiture Malou, Baxter Richard H G, Steinert Stefanie, Chelliah Yogarany, Frolet Cécile, Quispe-Tintaya Wilber, Hoffmann Jules A, Blandin Stéphanie A, Levashina Elena A
Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium Journal Article
In: Cell Host Microbe, vol. 5, no. 3, pp. 273–284, 2009, ISSN: 1934-6069.
Abstract | Links | BibTeX | Tags: Animals, Anopheles, APL1, Biological, blandin, Complement System Proteins, Hemolymph, hoffmann, Immunologic Factors, LRIM1, M3i, Models, Plasmodium, Protein Binding, Proteins, TEP1
@article{fraiture_two_2009,
title = {Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium},
author = {Malou Fraiture and Richard H G Baxter and Stefanie Steinert and Yogarany Chelliah and Cécile Frolet and Wilber Quispe-Tintaya and Jules A Hoffmann and Stéphanie A Blandin and Elena A Levashina},
doi = {10.1016/j.chom.2009.01.005},
issn = {1934-6069},
year = {2009},
date = {2009-03-01},
journal = {Cell Host Microbe},
volume = {5},
number = {3},
pages = {273--284},
abstract = {Plasmodium development within Anopheles mosquitoes is a vulnerable step in the parasite transmission cycle, and targeting this step represents a promising strategy for malaria control. The thioester-containing complement-like protein TEP1 and two leucine-rich repeat (LRR) proteins, LRIM1 and APL1, have been identified as major mosquito factors that regulate parasite loads. Here, we show that LRIM1 and APL1 are required for binding of TEP1 to parasites. RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium. LRIM1 and APL1 not only stabilize circulating TEP1, they also stabilize each other prior to their interaction with TEP1. Our results indicate that three major antiparasitic factors in mosquitoes jointly function as a complement-like system in parasite killing, and they reveal a role for LRR proteins as complement control factors.},
keywords = {Animals, Anopheles, APL1, Biological, blandin, Complement System Proteins, Hemolymph, hoffmann, Immunologic Factors, LRIM1, M3i, Models, Plasmodium, Protein Binding, Proteins, TEP1},
pubstate = {published},
tppubtype = {article}
}
2007
Winter F., Edaye S., Huttenhofer A., Brunel C.
Anopheles gambiae miRNAs as actors of defence reaction against Plasmodium invasion Journal Article
In: Nucleic Acids Res, vol. 35, no. 20, pp. 6953-62, 2007, (1362-4962 (Electronic) 0305-1048 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Abstract | BibTeX | Tags: *Gene, Animals, Anopheles, BRUNEL, Digestive, Expression, Female, gambiae/*genetics/*immunology/parasitology, Gene, III/genetics, Library, Male, MicroRNAs/*immunology, Plasmodium/*immunology, Profiling, Ribonuclease, silencing, System/immunology/metabolism/parasitology
@article{,
title = {Anopheles gambiae miRNAs as actors of defence reaction against Plasmodium invasion},
author = { F. Winter and S. Edaye and A. Huttenhofer and C. Brunel},
year = {2007},
date = {2007-01-01},
journal = {Nucleic Acids Res},
volume = {35},
number = {20},
pages = {6953-62},
abstract = {The path Plasmodium takes across the Anopheles midgut constitutes the major bottleneck during the malaria transmission cycle. In the present study, using a combination of shot-gun cloning and bioinformatic analysis, we have identified 18 miRNAs from Anopheles gambiae including three miRNAs unique to mosquito. Twelve of them are expressed ubiquitously across the body, independently of gender, while the other six exhibited an expression pattern restricted to the digestive system. Strikingly, the expression patterns of four miRNAs, including the three unique to mosquito, are affected by the presence of Plasmodium. We also show that knocking down Dicer1 and Ago1 mRNAs led to an increased sensitivity to Plasmodium infection. Altogether, these data support an involvement of miRNAs as new layers in the regulation of Anopheles defence reaction.},
note = {1362-4962 (Electronic)
0305-1048 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {*Gene, Animals, Anopheles, BRUNEL, Digestive, Expression, Female, gambiae/*genetics/*immunology/parasitology, Gene, III/genetics, Library, Male, MicroRNAs/*immunology, Plasmodium/*immunology, Profiling, Ribonuclease, silencing, System/immunology/metabolism/parasitology},
pubstate = {published},
tppubtype = {article}
}
2006
Shiao Shin-Hong, Whitten Miranda M A, Zachary Daniel, Hoffmann Jules A, Levashina Elena A
Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for Plasmodium killing in the mosquito midgut Journal Article
In: PLoS Pathog., vol. 2, no. 12, pp. e133, 2006, ISSN: 1553-7374.
Abstract | Links | BibTeX | Tags: Actins, Animals, Anopheles, Carrier Proteins, cdc42 GTP-Binding Protein, Double-Stranded, Electron, Frizzled Receptors, Gastrointestinal Tract, hoffmann, Host-Parasite Interactions, Immunity, Innate, Insect Vectors, Intestinal Mucosa, M3i, Melanins, Microarray Analysis, Microscopy, Plasmodium berghei, Polymers, Protozoan, RNA, scanning, telomerase
@article{shiao_fz2_2006,
title = {Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable for Plasmodium killing in the mosquito midgut},
author = {Shin-Hong Shiao and Miranda M A Whitten and Daniel Zachary and Jules A Hoffmann and Elena A Levashina},
doi = {10.1371/journal.ppat.0020133},
issn = {1553-7374},
year = {2006},
date = {2006-12-01},
journal = {PLoS Pathog.},
volume = {2},
number = {12},
pages = {e133},
abstract = {The midgut epithelium of the mosquito malaria vector Anopheles is a hostile environment for Plasmodium, with most parasites succumbing to host defenses. This study addresses morphological and ultrastructural features associated with Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. We show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. Dead or dying ookinetes are surrounded by a polymerized actin zone formed within the basal cytoplasm of adjacent host epithelial cells. In refractory strain mosquitoes, we found that formation of this zone is strongly linked to prophenoloxidase activation leading to melanization. Furthermore, we identify two factors controlling both phenomena: the transmembrane receptor frizzled-2 and the guanosine triphosphate-binding protein cell division cycle 42. However, the disruption of actin polymerization and melanization by double-stranded RNA inhibition did not affect ookinete survival. Our results separate the mechanisms of parasite killing from subsequent reactions manifested by actin polymerization and prophenoloxidase activation in the A. gambiae-P. berghei model. These latter processes are reminiscent of wound healing in other organisms, and we propose that they represent a form of wound-healing response directed towards a moribund ookinete, which is perceived as damaged tissue.},
keywords = {Actins, Animals, Anopheles, Carrier Proteins, cdc42 GTP-Binding Protein, Double-Stranded, Electron, Frizzled Receptors, Gastrointestinal Tract, hoffmann, Host-Parasite Interactions, Immunity, Innate, Insect Vectors, Intestinal Mucosa, M3i, Melanins, Microarray Analysis, Microscopy, Plasmodium berghei, Polymers, Protozoan, RNA, scanning, telomerase},
pubstate = {published},
tppubtype = {article}
}
2004
Imler Jean-Luc, Zheng Liangbiao
Biology of Toll receptors: lessons from insects and mammals Journal Article
In: Journal of Leukocyte Biology, vol. 75, no. 1, pp. 18–26, 2004, ISSN: 0741-5400.
Abstract | Links | BibTeX | Tags: Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors
@article{imler_biology_2004,
title = {Biology of Toll receptors: lessons from insects and mammals},
author = {Jean-Luc Imler and Liangbiao Zheng},
doi = {10.1189/jlb.0403160},
issn = {0741-5400},
year = {2004},
date = {2004-01-01},
journal = {Journal of Leukocyte Biology},
volume = {75},
number = {1},
pages = {18--26},
abstract = {Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.},
keywords = {Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Blandin Stephanie A, Shiao Shin-Hong, Moita Luis F, Janse Chris J, Waters Andrew P, Kafatos Fotis C, Levashina Elena A
Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae Journal Article
In: Cell, vol. 116, no. 5, pp. 661–670, 2004, ISSN: 0092-8674.
Abstract | BibTeX | Tags: Animals, Anopheles, blandin, Female, Genetic, Humans, Insect Proteins, Insect Vectors, M3i, Malaria, Models, Molecular, Plasmodium berghei, Polymorphism, Protein Structure, RNA, Sequence Alignment, Tertiary
@article{blandin_complement-like_2004,
title = {Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae},
author = {Stephanie A Blandin and Shin-Hong Shiao and Luis F Moita and Chris J Janse and Andrew P Waters and Fotis C Kafatos and Elena A Levashina},
issn = {0092-8674},
year = {2004},
date = {2004-01-01},
journal = {Cell},
volume = {116},
number = {5},
pages = {661--670},
abstract = {Anopheles mosquitoes are major vectors of human malaria in Africa. Large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. We report that the hemocyte-specific complement-like protein TEP1 from the mosquito Anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite Plasmodium berghei. The dsRNA knockdown of TEP1 in adults completely abolishes melanotic refractoriness in a genetically selected refractory strain. Moreover, in susceptible mosquitoes this knockdown increases the number of developing parasites. Our results suggest that the TEP1-dependent parasite killing is followed by a TEP1-independent clearance of dead parasites by lysis and/or melanization. Further elucidation of the molecular mechanisms of TEP1-mediated parasite killing will be of great importance for our understanding of the principles of vectorial capacity in insects.},
keywords = {Animals, Anopheles, blandin, Female, Genetic, Humans, Insect Proteins, Insect Vectors, M3i, Malaria, Models, Molecular, Plasmodium berghei, Polymorphism, Protein Structure, RNA, Sequence Alignment, Tertiary},
pubstate = {published},
tppubtype = {article}
}
Blandin Stéphanie A, Levashina Elena A
Mosquito immune responses against malaria parasites Journal Article
In: Curr. Opin. Immunol., vol. 16, no. 1, pp. 16–20, 2004, ISSN: 0952-7915.
Abstract | BibTeX | Tags: Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium
@article{blandin_mosquito_2004,
title = {Mosquito immune responses against malaria parasites},
author = {Stéphanie A Blandin and Elena A Levashina},
issn = {0952-7915},
year = {2004},
date = {2004-01-01},
journal = {Curr. Opin. Immunol.},
volume = {16},
number = {1},
pages = {16--20},
abstract = {Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis.},
keywords = {Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium},
pubstate = {published},
tppubtype = {article}
}
2002
Christophides George K, Zdobnov Evgeny, Barillas-Mury Carolina, Birney Ewan, Blandin Stephanie A, Blass Claudia, Brey Paul T, Collins Frank H, Danielli Alberto, Dimopoulos George, Hetru Charles, Hoa Ngo T, Hoffmann Jules A, Kanzok Stefan M, Letunic Ivica, Levashina Elena A, Loukeris Thanasis G, Lycett Gareth, Meister Stephan, Michel Kristin, Moita Luis F, Müller Hans-Michael, Osta Mike A, Paskewitz Susan M, Reichhart Jean-Marc, Rzhetsky Andrey, Troxler Laurent, Vernick Kenneth D, Vlachou Dina, Volz Jennifer, von Mering Christian, Xu Jiannong, Zheng Liangbiao, Bork Peer, Kafatos Fotis C
Immunity-related genes and gene families in Anopheles gambiae Journal Article
In: Science, vol. 298, no. 5591, pp. 159–165, 2002, ISSN: 1095-9203.
Abstract | Links | BibTeX | Tags: Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary
@article{christophides_immunity-related_2002,
title = {Immunity-related genes and gene families in Anopheles gambiae},
author = {George K Christophides and Evgeny Zdobnov and Carolina Barillas-Mury and Ewan Birney and Stephanie A Blandin and Claudia Blass and Paul T Brey and Frank H Collins and Alberto Danielli and George Dimopoulos and Charles Hetru and Ngo T Hoa and Jules A Hoffmann and Stefan M Kanzok and Ivica Letunic and Elena A Levashina and Thanasis G Loukeris and Gareth Lycett and Stephan Meister and Kristin Michel and Luis F Moita and Hans-Michael Müller and Mike A Osta and Susan M Paskewitz and Jean-Marc Reichhart and Andrey Rzhetsky and Laurent Troxler and Kenneth D Vernick and Dina Vlachou and Jennifer Volz and Christian von Mering and Jiannong Xu and Liangbiao Zheng and Peer Bork and Fotis C Kafatos},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12364793},
doi = {10.1126/science.1077136},
issn = {1095-9203},
year = {2002},
date = {2002-10-01},
journal = {Science},
volume = {298},
number = {5591},
pages = {159--165},
abstract = {We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.},
keywords = {Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary},
pubstate = {published},
tppubtype = {article}
}
2001
Vizioli J, Bulet Philippe, Hoffmann Jules A, Kafatos Fotis C, Müller H M, Dimopoulos G
Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 98, no. 22, pp. 12630–12635, 2001, ISSN: 0027-8424.
Abstract | Links | BibTeX | Tags: Animals, Anopheles, Anti-Bacterial Agents, Anti-Infective Agents, Base Sequence, Chromosome Mapping, hoffmann, Insect Proteins, Insect Vectors, M3i, Malaria, messenger, RNA
@article{vizioli_gambicin:_2001,
title = {Gambicin: a novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae},
author = {J Vizioli and Philippe Bulet and Jules A Hoffmann and Fotis C Kafatos and H M Müller and G Dimopoulos},
doi = {10.1073/pnas.221466798},
issn = {0027-8424},
year = {2001},
date = {2001-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {98},
number = {22},
pages = {12630--12635},
abstract = {A novel mosquito antimicrobial peptide, gambicin, and the corresponding gene were isolated in parallel through differential display-PCR, an expressed sequence tag (EST) project, and characterization of an antimicrobial activity in a mosquito cell line by reverse-phase chromatography. The 616-bp gambicin ORF encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide bridges. Gambicin lacks sequence homology with other known proteins. Like other Anopheles gambiae antimicrobial peptide genes, gambicin is induced by natural or experimental infection in the midgut, fatbody, and hemocyte-like cell lines. Within the midgut, gambicin is predominantly expressed in the anterior part. Both local and systemic gambicin expression is induced during early and late stages of natural malaria infection. In vitro experiments showed that the 6.8-kDa mature peptide can kill both Gram-positive and Gram-negative bacteria, has a morphogenic effect on a filamentous fungus, and is marginally lethal to Plasmodium berghei ookinetes. An oxidized form of gambicin isolated from the cell line medium was more active against bacteria than the nonoxidized form from the same medium.},
keywords = {Animals, Anopheles, Anti-Bacterial Agents, Anti-Infective Agents, Base Sequence, Chromosome Mapping, hoffmann, Insect Proteins, Insect Vectors, M3i, Malaria, messenger, RNA},
pubstate = {published},
tppubtype = {article}
}
Levashina Elena A, Moita L F, Blandin Stéphanie A, Vriend G, Lagueux Marie, Kafatos F C
Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae Journal Article
In: Cell, vol. 104, no. 5, pp. 709–718, 2001, ISSN: 0092-8674.
Abstract | BibTeX | Tags: alpha-Macroglobulins, Animals, Anopheles, blandin, Cells, Cloning, Complement C3, Cultured, DNA Fragmentation, Double-Stranded, Female, Genetic, Gram-Negative Bacteria, Hemocytes, Insect Proteins, M3i, Molecular, Nucleic Acid Denaturation, Phagocytosis, Protein Structure, RNA, Tertiary, Transcription
@article{levashina_conserved_2001,
title = {Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae},
author = {Elena A Levashina and L F Moita and Stéphanie A Blandin and G Vriend and Marie Lagueux and F C Kafatos},
issn = {0092-8674},
year = {2001},
date = {2001-01-01},
journal = {Cell},
volume = {104},
number = {5},
pages = {709--718},
abstract = {We characterize a novel hemocyte-specific acute phase glycoprotein from the malaria vector, Anopheles gambiae. It shows substantial structural and functional similarities, including the highly conserved thioester motif, to both a central component of mammalian complement system, factor C3, and to a pan-protease inhibitor, alpha2-macroglobulin. Most importantly, this protein serves as a complement-like opsonin and promotes phagocytosis of some Gram-negative bacteria in a mosquito hemocyte-like cell line. Chemical inactivation by methylamine and depletion by double-stranded RNA knockout demonstrate that this function is dependent on the internal thioester bond. This evidence of a complement-like function in a protostome animal adds substantially to the accumulating evidence of a common ancestry of immune defenses in insects and vertebrates.},
keywords = {alpha-Macroglobulins, Animals, Anopheles, blandin, Cells, Cloning, Complement C3, Cultured, DNA Fragmentation, Double-Stranded, Female, Genetic, Gram-Negative Bacteria, Hemocytes, Insect Proteins, M3i, Molecular, Nucleic Acid Denaturation, Phagocytosis, Protein Structure, RNA, Tertiary, Transcription},
pubstate = {published},
tppubtype = {article}
}
1999
Lowenberger C A, Kamal S, Chiles J, Paskewitz S, Bulet Philippe, Hoffmann Jules A, Christensen B M
Mosquito-Plasmodium interactions in response to immune activation of the vector Journal Article
In: Exp. Parasitol., vol. 91, no. 1, pp. 59–69, 1999, ISSN: 0014-4894.
Abstract | Links | BibTeX | Tags: Aedes, Animals, Anopheles, Culicidae, Defensins, Digestive System, Escherichia coli, Female, Genetic, Hemolymph, hoffmann, Insect Vectors, M3i, messenger, Micrococcus luteus, Plasmodium, Plasmodium berghei, Plasmodium gallinaceum, Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, Transcription
@article{lowenberger_mosquito-plasmodium_1999,
title = {Mosquito-Plasmodium interactions in response to immune activation of the vector},
author = {C A Lowenberger and S Kamal and J Chiles and S Paskewitz and Philippe Bulet and Jules A Hoffmann and B M Christensen},
doi = {10.1006/expr.1999.4350},
issn = {0014-4894},
year = {1999},
date = {1999-01-01},
journal = {Exp. Parasitol.},
volume = {91},
number = {1},
pages = {59--69},
abstract = {During the development of Plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. The elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. We demonstrate here that if Aedes aegypti or Anopheles gambiae, normally susceptible to Plasmodium gallinaceum and P. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodmeal, there is a significant reduction in the prevalence and mean intensity of infection of oocysts on the midgut. Only those mosquitoes immune activated prior to, or immediately after, parasite ingestion exhibit this reduction in parasite development. Mosquitoes immune activated 2-5 days after bloodfeeding show no differences in parasite burdens compared with naive controls. Northern analyses reveal that transcriptional activity for mosquito defensins is not detected in the whole bodies of Ae. aegypti from 4 h to 10 days after ingesting P. gallinaceum, suggesting that parasite ingestion, passage from the food bolus through the midgut, oocyst formation, and subsequent release of sporozoites into the hemolymph do not induce the production of defensin. However, reverse transcriptase-PCR of RNA isolated solely from the midguts of Ae. aegypti indicates that transcription of mosquito defensins occurs in the midguts of naive mosquitoes and those ingesting an infectious or noninfectious bloodmeal. Bacteria-challenged Ae. aegypti showed high levels of mature defensin in the hemolymph that correlate with a lower prevalence and mean intensity of infection with oocysts. Because few oocysts were found on the midgut of immune-activated mosquitoes, the data suggest that some factor, induced by bacterial challenge, kills the parasite at a preoocyst stage.},
keywords = {Aedes, Animals, Anopheles, Culicidae, Defensins, Digestive System, Escherichia coli, Female, Genetic, Hemolymph, hoffmann, Insect Vectors, M3i, messenger, Micrococcus luteus, Plasmodium, Plasmodium berghei, Plasmodium gallinaceum, Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, Transcription},
pubstate = {published},
tppubtype = {article}
}
1997
Hoffmann Jules A
Immune responsiveness in vector insects Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 94, no. 21, pp. 11152–11153, 1997, ISSN: 0027-8424.
BibTeX | Tags: Animals, Anopheles, bacteria, Blood Proteins, Defensins, hoffmann, Humans, Insect Vectors, Life Cycle Stages, M3i, Malaria, Mammals, Plasmodium
@article{hoffmann_immune_1997,
title = {Immune responsiveness in vector insects},
author = {Jules A Hoffmann},
issn = {0027-8424},
year = {1997},
date = {1997-10-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {94},
number = {21},
pages = {11152--11153},
keywords = {Animals, Anopheles, bacteria, Blood Proteins, Defensins, hoffmann, Humans, Insect Vectors, Life Cycle Stages, M3i, Malaria, Mammals, Plasmodium},
pubstate = {published},
tppubtype = {article}
}
1996
Barillas-Mury Carolina, Charlesworth A, Gross I, Richman A, Hoffmann Jules A, Kafatos Fotis C
Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae Journal Article
In: EMBO J., vol. 15, no. 17, pp. 4691–4701, 1996, ISSN: 0261-4189.
Abstract | BibTeX | Tags: Amino Acid, Animals, Anopheles, Base Sequence, Biological Transport, Cell Nucleus, Cells, Complementary, Cultured, DNA, DNA-Binding Proteins, hoffmann, Insect Proteins, Insect Vectors, M3i, NF-kappa B, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Sequence Homology, Trans-Activators, Transcriptional Activation
@article{barillas-mury_immune_1996,
title = {Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae},
author = {Carolina Barillas-Mury and A Charlesworth and I Gross and A Richman and Jules A Hoffmann and Fotis C Kafatos},
issn = {0261-4189},
year = {1996},
date = {1996-09-01},
journal = {EMBO J.},
volume = {15},
number = {17},
pages = {4691--4701},
abstract = {A novel rel family member, Gambif1 (gambiae immune factor 1), has been cloned from the human malaria vector, Anopheles gambiae, and shown to be most similar to Drosophila Dorsal and Dif. Gambif1 protein is translocated to the nucleus in fat body cells in response to bacterial challenge, although the mRNA is present at low levels at all developmental stages and is not induced by infection. DNA binding activity to the kappaB-like sites in the A.gambiae Defensin and the Drosophila Diptericin and Cecropin promoters is also induced in larval nuclear extracts following infection. Gambif1 has the ability to bind to kappaB-like sites in vitro. Co-transfection assays in Drosophila mbn-2 cells show that Gambif1 can activate transcription by interacting with the Drosophila Diptericin regulatory elements, but is not functionally equivalent to Dorsal in this assay. Gambif1 protein translocation to the nucleus and the appearance of kappaB-like DNA binding activity can serve as molecular markers of activation of the immune system and open up the possibility of studying the role of defence reactions in determining mosquito susceptibility/refractoriness to malaria infection.},
keywords = {Amino Acid, Animals, Anopheles, Base Sequence, Biological Transport, Cell Nucleus, Cells, Complementary, Cultured, DNA, DNA-Binding Proteins, hoffmann, Insect Proteins, Insect Vectors, M3i, NF-kappa B, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Sequence Homology, Trans-Activators, Transcriptional Activation},
pubstate = {published},
tppubtype = {article}
}
Richman A M, Bulet Philippe, Hetru Charles, Barillas-Mury Carolina, Hoffmann Jules A, Kafalos Fotis C
Inducible immune factors of the vector mosquito Anopheles gambiae: biochemical purification of a defensin antibacterial peptide and molecular cloning of preprodefensin cDNA Journal Article
In: Insect Mol. Biol., vol. 5, no. 3, pp. 203–210, 1996, ISSN: 0962-1075.
Abstract | BibTeX | Tags: Amino Acid, Animals, Anopheles, Base Sequence, Blood Bactericidal Activity, Blood Proteins, Cloning, Complementary, Defensins, DNA, Escherichia coli, Female, Gene Expression, Genes, hoffmann, Insect, Insect Vectors, Larva, M3i, Micrococcus luteus, Molecular, Sequence Homology
@article{richman_inducible_1996,
title = {Inducible immune factors of the vector mosquito Anopheles gambiae: biochemical purification of a defensin antibacterial peptide and molecular cloning of preprodefensin cDNA},
author = {A M Richman and Philippe Bulet and Charles Hetru and Carolina Barillas-Mury and Jules A Hoffmann and Fotis C Kafalos},
issn = {0962-1075},
year = {1996},
date = {1996-08-01},
journal = {Insect Mol. Biol.},
volume = {5},
number = {3},
pages = {203--210},
abstract = {Larvae of the mosquito vector of human malaria, Anopheles gambiae, were inoculated with bacteria and extracts were biochemically fractionated by reverse-phase HPLC. Multiple induced polypeptides and antibacterial activities were observed following bacterial infection, including a member of the insect defensin family of antibacterial proteins. A cDNA encoding An. gambiae preprodefensin was isolated using PCR primers based on phylogenetically conserved sequences. The mature peptide is highly conserved, but the signal and propeptide segments are not, relative to corresponding defensin sequences of other insects. Defensin expression is induced in response to bacterial infection, in both adult and larval stages. In contrast, pupae express defensin mRNA constitutively. Defensin expression may prove a valuable molecular marker to monitor the An. gambiae host response to infection by parasitic protozoa of medical importance.},
keywords = {Amino Acid, Animals, Anopheles, Base Sequence, Blood Bactericidal Activity, Blood Proteins, Cloning, Complementary, Defensins, DNA, Escherichia coli, Female, Gene Expression, Genes, hoffmann, Insect, Insect Vectors, Larva, M3i, Micrococcus luteus, Molecular, Sequence Homology},
pubstate = {published},
tppubtype = {article}
}