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@article{ferreira_small_2018,

title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis},

author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques},

doi = {10.1371/journal.pntd.0006569},

issn = {1935-2735},

year  = {2018},

date = {2018-01-01},

journal = {PLoS Negl Trop Dis},

volume = {12},

number = {6},

pages = {e0006569},

abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.},

keywords = {Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@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}

}

@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}

}

@article{hoffmann_phylogenetic_1999,

title = {Phylogenetic perspectives in innate immunity},

author = {Jules A Hoffmann and Fotis C Kafatos and Charles A Janeway and Alan R B Ezekowitz},

issn = {0036-8075},

year  = {1999},

date = {1999-05-01},

journal = {Science},

volume = {284},

number = {5418},

pages = {1313--1318},

abstract = {The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity.},

keywords = {Active, Animals, Culicidae, hoffmann, Humans, Immunity, Immunological, infection, Innate, Insect Vectors, M3i, Mammals, Models, Phagocytosis, Phylogeny, Proteins},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{shahabuddin_plasmodium_1998,

title = {Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin},

author = {M Shahabuddin and I Fields and Philippe Bulet and Jules A Hoffmann and L H Miller},

doi = {10.1006/expr.1998.4212},

issn = {0014-4894},

year  = {1998},

date = {1998-05-01},

journal = {Exp. Parasitol.},

volume = {89},

number = {1},

pages = {103--112},

abstract = {We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium.},

keywords = {Aedes, Animals, Anti-Infective Agents, Blood Proteins, Defensins, Diptera, hoffmann, Insect Vectors, insects, M3i, Plasmodium gallinaceum, Zygote},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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}

}

@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}

}

@article{lowenberger_insect_1995,

title = {Insect immunity: isolation of three novel inducible antibacterial defensins from the vector mosquito, Aedes aegypti},

author = {C Lowenberger and Philippe Bulet and Maurice Charlet and Charles Hetru and B Hodgeman and B M Christensen and Jules A Hoffmann},

issn = {0965-1748},

year  = {1995},

date = {1995-07-01},

journal = {Insect Biochem. Mol. Biol.},

volume = {25},

number = {7},

pages = {867--873},

abstract = {The injection of Escherichia coli and Micrococcus luteus into the hemocoel of Aedes aegypti induces a potent antibacterial activity in the hemolymph. We have purified and fully characterized three 40-residue antibacterial peptides from the hemolymph of bacteria-challenged mosquitoes that are absent in naive mosquitoes. The peptides are potently active against Gram-positive bacteria and against one of the Gram-negative bacteria that were tested. The amino acid sequences clearly show that the three peptides are novel isoforms of the insect defensin family of antibacterial peptides. They differ from each other by one or two amino acid residues. We present here the complete amino acid sequences of the three isoforms and the activity spectrum of the predominant Aedes defensin.},

keywords = {Aedes, Amino Acid, Animals, Anti-Bacterial Agents, Blood Proteins, Defensins, Escherichia coli, Gram-Negative Bacteria, Gram-Positive Bacteria, hoffmann, Immunity, Insect Vectors, M3i, Micrococcus luteus, Sequence Homology, Stereoisomerism},

pubstate = {published},

tppubtype = {article}

}