Pathogenesis of bacterial infections and immunity

@article{pmid37876025,

title = {Ascorbate deficiency increases progression of shigellosis in guinea pigs and mice infection models},

author = {Jurate Skerniskyte and Céline Mulet and Antonin C André and Mark C Anderson and Louise Injarabian and Achim Buck and Verena M Prade and Philippe J Sansonetti and Sophie Reibel-Foisset and Axel K Walch and Michel Lebel and Jens Lykkesfeldt and Benoit S Marteyn},

doi = {10.1080/19490976.2023.2271597},

issn = {1949-0984},

year  = {2023},

date = {2023-12-01},

urldate = {2023-12-01},

journal = {Gut Microbes},

volume = {15},

number = {2},

pages = {2271597},

abstract = { spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of  entire life cycle  and the evaluation of vaccine candidates' protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon  oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to  infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested (,  5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although  was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased  penetration into the colon epithelium layer in a Gulo mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both  infection strategies and immune responses to  infection.},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37806286,

title = {Escherichia coli killing by epidemiologically successful sublineages of Shigella sonnei is mediated by colicins},

author = {P Malaka De Silva and Rebecca J Bennett and Lauriane Kuhn and Patryk Ngondo and Lorine Debande and Elisabeth Njamkepo and Brian Ho and François-Xavier Weill and Benoît S Marteyn and Claire Jenkins and Kate S Baker},

doi = {10.1016/j.ebiom.2023.104822},

issn = {2352-3964},

year  = {2023},

date = {2023-10-01},

urldate = {2023-10-01},

journal = {EBioMedicine},

volume = {97},

pages = {104822},

abstract = {BACKGROUND: Shigella sp. are enteric pathogens which causes >125 million cases of shigellosis annually. S. sonnei accounts for about a quarter of those cases and is increasingly prevalent in industrialising nations. Being an enteric pathogen, S. sonnei benefits from outcompeting gut commensals such as Escherichia coli to establish itself and cause disease. There are numerous mechanisms that bacterial pathogens use to outcompete its rivals including molecules called colicins. A Type 6 Secretion System (T6SS) was recently described as contributing to E. coli killing in S. sonnei.nnMETHODS: We used Bulk Phenotyping of Epidemiological Replicates (BPER) which combined bacterial Genome Wide Association Studies (bGWAS) and high throughput phenotyping on a collection of S. sonnei surveillance isolates to identify the genetic features associated with E. coli killing and explore their relationship with epidemiological behaviour. We further explored the presence of colicins and T6SS components in the isolates using genomics, laboratory experimentation, and proteomics.nnFINDINGS: Our bGWAS analysis returned known and novel colicin and colicin related genes as significantly associated with E. coli killing. In silico analyses identified key colicin clusters responsible for the killing phenotype associated with epidemiologically successful sub-lineages. The killing phenotype was not associated with the presence of a T6SS. Laboratory analyses confirmed the presence of the key colicin clusters and that killing was contact-independent.nnINTERPRETATION: Colicins are responsible for E. coli killing by S. sonnei, not a T6SS. This phenotype contributes to shaping the observed epidemiology of S. sonnei and may contribute to its increasing prevalence globally. BPER is an epidemiologically relevant approach to phenotypic testing that enables the rapid identification of genetic drivers of phenotypic changes, and assessment of their relevance to epidemiology in natural settings.nnFUNDING: Biotechnology and Biological Sciences Research Council, Biotechnology and Biological Sciences Research Council Doctoral Training Partnership studentship, Wellcome Trust, Medical Research Council (UK), French National Research Agency.},

keywords = {MARTEYN, PPSE, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37267103,

title = {The E3 ubiquitin ligase FBXL6 controls the quality of newly synthesized mitochondrial ribosomal proteins},

author = {Julie Lavie and Claude Lalou and Walid Mahfouf and Jean-William Dupuy and Aurélie Lacaule and Agata Ars Cywinska and Didier Lacombe and Anne-Marie Duchêne and Anne-Aurélie Raymond and Hamid Reza Rezvani and Richard Patryk Ngondo and Giovanni Bénard},

doi = {10.1016/j.celrep.2023.112579},

issn = {2211-1247},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Cell Rep},

volume = {42},

number = {6},

pages = {112579},

abstract = {In mammals, about 99% of mitochondrial proteins are synthesized in the cytosol as precursors that are subsequently imported into the organelle. The mitochondrial health and functions rely on an accurate quality control of these imported proteins. Here, we show that the E3 ubiquitin ligase F box/leucine-rich-repeat protein 6 (FBXL6) regulates the quality of cytosolically translated mitochondrial proteins. Indeed, we found that FBXL6 substrates are newly synthesized mitochondrial ribosomal proteins. This E3 binds to chaperones involved in the folding and trafficking of newly synthesized peptide and to ribosomal-associated quality control proteins. Deletion of these interacting partners is sufficient to hamper interactions between FBXL6 and its substrate. Furthermore, we show that cells lacking FBXL6 fail to degrade specifically mistranslated mitochondrial ribosomal proteins. Finally, showing the role of FBXL6-dependent mechanism, FBXL6-knockout (KO) cells display mitochondrial ribosomal protein aggregations, altered mitochondrial metabolism, and inhibited cell cycle in oxidative conditions.},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36167663,

title = {CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival},

author = {Camille Danne and Chloé Michaudel and Jurate Skerniskyte and Julien Planchais and Aurélie Magniez and Allison Agus and Marie-Laure Michel and Bruno Lamas and Gregory Da Costa and Madeleine Spatz and Cyriane Oeuvray and Chloé Galbert and Maxime Poirier and Yazhou Wang and Alexia Lapière and Nathalie Rolhion and Tatiana Ledent and Cédric Pionneau and Solenne Chardonnet and Floriant Bellvert and Edern Cahoreau and Amandine Rocher and Rafael Rose Arguello and Carole Peyssonnaux and Sabine Louis and Mathias L Richard and Philippe Langella and Jamel El-Benna and Benoit Marteyn and Harry Sokol},

doi = {10.1136/gutjnl-2022-326917},

issn = {1468-3288},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {Gut},

volume = {72},

issue = {6},

pages = {1081-1092},

abstract = {OBJECTIVES: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown.



DESIGN: We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of  deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real-time bioenergetic profile analysis (Seahorse).



RESULTS: Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction increases mitochondrial reactive oxygen species production leading to the premature death of neutrophilsthrough apoptosis, especially in oxidative environment. The decreased functional neutrophils in tissues might explain the impaired containment of fungi and increased susceptibility to intestinal inflammation.



CONCLUSION: These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The battle for oxygen during bacterial and fungal infections},

author = {A. C. Andre and M. Laborde and B. S. Marteyn},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=35131160},

doi = {10.1016/j.tim.2022.01.002},

isbn = {35131160},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Trends Microbiol},

volume = {30},

issue = {7},

pages = {643-653},

abstract = {Bacterial and fungal pathogens face various microenvironmental conditions during infection. In addition to acidosis, nutrient consumption, and hypercapnia, pathogen infections are associated with hypoxia, which is induced by bacterial and fungal respiration during the formation of foci of infection or biofilms. Consequently, the in vivo interaction between host immune cells and pathogens is anticipated to occur mainly under low-oxygen conditions. Various infectious disease models have reported that pathogens benefit from hypoxia, which dampens the oxygen-dependent antimicrobial activities of macrophages and neutrophils, such as the production of reactive oxygen species (ROS). Due to their dual respiration capacity (aerobic and anaerobic) or phenotypical adaptation (e.g., dormancy), pathogens have the capacity to survive and disseminate in the absence of oxygen. In addition, hypoxia modulates various mechanisms of pathogen virulence, promoting the dissemination of pathogens. Further investigations are still required to evaluate the relative importance of oxygen on the capacity of pathogens to invade and colonize host organs and to better understand alternative strategies developed by immune cells to circumvent pathogen dissemination in the absence of oxygen. Addressing this important and fundamental question in various models of infection may direct the development of innovative therapeutic strategies.},

note = {1878-4380 (Electronic) 

0966-842X (Linking) 

Journal Article 

Review},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{Andre2021,

title = {The selective advantage of facultative anaerobes relies on their unique ability to cope with changing oxygen levels during infection},

author = {A C Andre and L Debande and B S Marteyn},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=33813807},

doi = {10.1111/cmi.13338},

isbn = {33813807},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Cell Microbiol},

volume = {23},

number = {8},

pages = {e13338},

abstract = {Bacteria, including those that are pathogenic, have been generally classified according to their ability to survive and grow in the presence or absence of oxygen: aerobic and anaerobic bacteria, respectively. Strict aerobes require oxygen to grow (e.g. Neisseria), and strict anaerobes grow exclusively without, and do not survive oxygen exposure (e.g. Clostridia); aerotolerant bacteria (e.g. Lactobacilli) are insensitive to oxygen exposure. Facultative anaerobes (e.g. E. coli) have the unique ability to grow in the presence or in the absence of oxygen. and are thus well-adapted to these changing conditions which may constitute an underestimated selective advantage for infection. In the WHO antibiotic-resistant "priority pathogens" list, facultative anaerobes are overrepresented (8 among 12 listed pathogens), consistent with clinical studies performed in populations particularly susceptible to infectious diseases. Bacteria aerobic respiratory chain plays a central role in oxygen consumption, leading to the formation of hypoxic infectious sites (infectious hypoxia). Facultative anaerobes have developed a wide diversity of aerotolerance and anaerotolerance strategies in vivo. However, at a single cell level, the modulation of the intracellular oxygen level in host infected cells remains elusive and will be discussed in this review. In conclusion, the ability of facultative bacteria to evolve in the presence or the absence of oxygen is essential for their virulence strategy and constitute a selective advantage. This article is protected by copyright. All rights reserved.},

note = {1462-5822 (Electronic) 

1462-5814 (Linking) 

Journal Article 

Review},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{Injarabian2021,

title = {Reducing neutrophil exposure to oxygen allows their basal state maintenance},

author = {L Injarabian and J Skerniskyte and Q G Gianetto and V Witko-Sarsat and B S Marteyn},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=33811670},

doi = {10.1111/imcb.12458},

isbn = {33811670},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Immunol Cell Biol},

volume = {99},

number = {7},

pages = {782-789},

abstract = {Neutrophils are the most abundant circulating white blood cells and are the central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1-4% O2), to which they are well adapted. Neutrophils are atypical cells since they are highly glycolytic, and susceptible to oxygen exposure, which induces their activation and death, through mechanisms, which remain currently elusive. Nevertheless, nearly all studies conducted on neutrophils are carried out under atmospheric oxygen (21%), corresponding to hyperoxia. Here, we investigated the impact of hyperoxia during neutrophil purification and culture on neutrophil viability, activation and cytosolic protein content. We demonstrate that neutrophil hyper-activation (CD62L shedding) is induced during culture under hyperoxic conditions (24 h), compared to neutrophils cultured under anoxic conditions. Spontaneous neutrophil extracellular trap (NET) formation is observed when neutrophils face hyperoxia during purification or culture. In addition, we show that maintaining neutrophils in autologous plasma is the preferred strategy to maintain their basal state. Our results show that manipulating neutrophils under hyperoxic conditions leads to the loss of 57 cytosolic proteins during purification, while it does not lead to an immediate impact on neutrophil activation (CD11b(high), CD54(high), CD62L(neg)) or viability (DAPI(+)). We identified two clusters of proteins belonging to the cholesterol metabolism and to the complement and coagulation cascade pathways, which are highly susceptible to neutrophil oxygen exposure during neutrophil purification. In conclusion, protecting neutrophil from oxygen during their purification and culture is recommended to avoid activation and prevent the alteration cytosolic protein composition.},

note = {1440-1711 (Electronic) 

0818-9641 (Linking) 

Journal Article},

keywords = {Activation, anoxia, hyperoxia, MARTEYN, neutrophils, Unité ARN, viability},

pubstate = {published},

tppubtype = {article}

}

@article{Skerniskyte2021,

title = {OmpA Protein-Deficient Acinetobacter baumannii Outer Membrane Vesicles Trigger Reduced Inflammatory Response},

author = {J Skerniskyte and E Karazijaite and A Luciunaite and E Suziedeliene},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=33807410},

doi = {10.3390/pathogens10040407},

isbn = {33807410},

year  = {2021},

date = {2021-01-01},

journal = {Pathogens},

volume = {10},

number = {4},

pages = {407},

abstract = {Multidrug resistant Acinetobacter baumannii shows a growing number of nosocomial infections worldwide during the last decade. The outer membrane vesicles (OMVs) produced by this bacterium draw increasing attention as a possible treatment target. OMVs have been implicated in the reduction of antibiotic level in the surrounding environment, transfer of virulence factors into the host cells, and induction of inflammatory response. Although the evidence on the involvement of OMVs in A. baumannii pathogenesis is currently growing, their role during inflammation is insufficiently explored. It is likely that bacteria, by secreting OMVs, can expand the area of their exposure and prepare surrounding matrix for infection. Here, we investigated the impact of A. baumannii OMVs on activation of macrophages in vitro. We show that OmpA protein present in A. baumannii OMVs substantially contributes to the proinflammatory response in J774 murine macrophages and to the cell death in both lung epithelium cells and macrophages. The loss of OmpA protein in OMVs, obtained from A. baumannii ompA mutant, resulted in the altered expression of genes coding for IL-6, NLRP3 and IL-1beta proinflammatory molecules in macrophages in vitro. These results imply that OmpA protein in bacterial OMVs could trigger a more intense proinflammatory response.},

note = {2076-0817 (Print) 

2076-0817 (Linking) 

Journal Article},

keywords = {Acinetobacter baumannii, inflammasome, inflammation, Macrophages, MARTEYN, outer membrane vesicles, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Vitamin C levels in a Central-African mother-infant cohort: Does hypovitaminosis C increase the risk of enteric infections?},

author = {V Moya-Alvarez and J J Koyembi and L M Kaye and J R Mbecko and H Sanke-Waigana and S G Djorie and Y T Nyasenu and D Mad-Bondo and J B Kongoma and S Nakib and Y Madec and G Ulmann and N Neveux and P J Sansonetti and M Vray and B Marteyn},

url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=34137176},

doi = {10.1111/mcn.13215},

isbn = {34137176},

year  = {2021},

date = {2021-01-01},

journal = {Matern Child Nutr},

pages = {e13215},

abstract = {In the MITICA (Mother-to-Infant TransmIssion of microbiota in Central-Africa) study, 48 mothers and their 50 infants were followed from delivery to 6 months between December 2017 and June 2019 in Bangui (Central-African Republic). Blood tests and stool analyses were performed in mothers at delivery, and their offspring at birth, 11 weeks and 25 weeks. Stool cultures were performed in specific growth media for Salmonella, Shigella, E. coli, Campylobacter, Enerobacter, Vibrio cholerae, Citrobacter and Klebsiella, as well as rotavirus, yeasts and parasitological exams. The median vitamin C levels in mothers at delivery were 15.3 mumol/L (inter-quartile-range [IQR] 6.2-27.8 mumol/L). In infants, the median vitamin C levels at birth were 35.2 mumol/L (IQR 16.5-63.9 mumol/L). At 11 and 25 weeks, the median vitamin C levels were 41.5 mumol/L (IQR 18.7-71.6 mumol/L) and 18.2 mumol/L (IQR 2.3-46.6 mumol/L), respectively. Hypovitaminosis C was defined as seric vitamin C levels <28 mumol/L and vitamin C deficiency was defined as vitamin C levels <11 mumol/L according to the WHO definition. In mothers, the prevalence of hypovitaminosis-C and vitamin C deficiency at delivery was 34/45 (75.6%) and 19/45 (42.2%), respectively. In infants, the prevalence of hypovitaminosis-C and vitamin C deficiency at 6 months was 18/33 (54.6%) and 11/33 (33.3%), respectively. Vitamin C levels in mothers and infants were correlated at birth (Spearman's rho = 0.5; P value = 0.002), and infants had significantly higher levels of vitamin C (median = 35.2 mumol/L; IQR 16.5-63.9 mumol/L), compared to mothers (median = 15.3 mumol/L; IQR 6.2-27.8 mumol/L; P value <0.001). The offspring of vitamin C-deficient mothers had significantly lower vitamin C levels at delivery (median = 18.7 mumol/L; IQR 13.3-30.7 mumol/L), compared to the offspring of non-deficient mothers (median = 62.2 mumol/L; IQR 34.6-89.2 mumol/L; P value <0.001). Infants with hypovitaminosis-C were at significantly higher risk of having a positive stool culture during the first 6 months of life (adjusted OR = 5.3, 95% CI 1.1; 26.1; P value = 0.038).},

note = {1740-8709 (Electronic) 

1740-8695 (Linking) 

Journal Article},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Ascorbate maintains a low plasma oxygen level},

author = {L Injarabian and M Scherlinger and A Devin and S Ransac and J Lykkesfeldt and B S Marteyn},

url = {https://pubmed.ncbi.nlm.nih.gov/32606354/},

doi = {10.1038/s41598-020-67778-w},

isbn = {32606354},

year  = {2020},

date = {2020-01-01},

journal = {Sci Rep},

volume = {10},

number = {1},

pages = {10659},

abstract = {In human blood, oxygen is mainly transported by red blood cells. Accordingly, the dissolved oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that human plasma pO2 = 8.4 mmHg (1.1% O2). Oxygen solubility in plasma was believed to be similar to water. Here we reveal that plasma has an additional ascorbate-dependent oxygen-reduction activity. Plasma experimental oxygenation oxidizes ascorbate (49.5 μM in fresh plasma vs < 2 μM in oxidized plasma) and abolishes this capacity, which is restored by ascorbate supplementation. We confirmed these results in vivo, showing that the plasma pO2 is significantly higher in ascorbate-deficient guinea pigs (Ascorbateplasma < 2 μM), compared to control (Ascorbateplasma > 15 μM). Plasma low oxygen level preserves the integrity of oxidation-sensitive components such as ubiquinol. Circulating leucocytes are well adapted to these conditions, since the abundance of their mitochondrial network is limited. These results shed a new light on the importance of oxygen exposure on leucocyte biological study, in regards with the reducing conditions they encounter in vivo; but also, on the manipulation of blood products to improve their integrity and potentially improve transfusions' efficacy.},

keywords = {MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Mapping of Shigella flexneri's tissue distribution and type III secretion apparatus activity during infection of the large intestine of guinea pigs},

author = {G Nigro and E T Arena and M Sachse and M Moya-Nilges and B S Marteyn and P J Sansonetti and F X Campbell-Valois},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31578543},

doi = {10.1093/femspd/ftz054},

isbn = {31578543},

year  = {2019},

date = {2019-01-01},

journal = {Pathog Dis},

volume = {77},

number = {7},

pages = {ftz054},

abstract = {Shigella spp. are bacterial pathogens that invade the human colonic mucosa using a type III secretion apparatus (T3SA), a proteinaceous device activated upon contact with host cells. Active T3SAs translocate proteins that carve the intracellular niche of Shigella spp. Nevertheless, the activation state of the T3SA has not been addressed in vivo. Here, we used a green fluorescent protein transcription-based secretion activity reporter (TSAR) to provide a spatio-temporal description of S. flexneri T3SAs activity in the colon of Guinea pigs. First, we observed that early mucus release is triggered in the vicinity of luminal bacteria with inactive T3SA. Subsequent mucosal invasion showed bacteria with active T3SA associated with the brush border, eventually penetrating into epithelial cells. From 2 to 8 h post-challenge, the infection foci expanded, and these intracellular bacteria displayed homogeneously high-secreting activity, while extracellular foci within the lamina propria featured bacteria with low secretion activity. We also found evidence that within lamina propria macrophages, bacteria reside in vacuoles instead of accessing the cytosol. Finally, bacteria were cleared from tissues between 8 and 24 h post-challenge, highlighting the hit-and-run colonization strategy of Shigella. This study demonstrates how genetically encoded reporters can contribute to deciphering pathogenesis in vivo.},

keywords = {MARTEYN, Shigella in vivo infection fluorescence microscopy genetically encoded reporters large intestine type III secretion system, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{,

title = {Neutrophil Metabolic Shift during their Lifecycle: Impact on their Survival and Activation},

author = {L Injarabian and A Devin and S Ransac and B S Marteyn},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31906243?dopt=Abstract},

doi = {10.3390/ijms21010287},

isbn = {31906243},

year  = {2019},

date = {2019-01-01},

journal = {Int J Mol Sci},

volume = {21},

number = {1},

pages = {287},

abstract = {Polymorphonuclear neutrophils (PMNs) are innate immune cells, which represent 50% to 70% of the total circulating leukocytes. How PMNs adapt to various microenvironments encountered during their life cycle, from the bone marrow, to the blood plasma fraction, and to inflamed or infected tissues remains largely unexplored. Metabolic shifts have been reported in other immune cells such as macrophages or lymphocytes, in response to local changes in their microenvironment, and in association with a modulation of their pro-inflammatory or anti-inflammatory functions. The potential contribution of metabolic shifts in the modulation of neutrophil activation or survival is anticipated even though it is not yet fully described. If neutrophils are considered to be mainly glycolytic, the relative importance of alternative metabolic pathways, such as the pentose phosphate pathway, glutaminolysis, or the mitochondrial oxidative metabolism, has not been fully considered during activation. This statement may be explained by the lack of knowledge regarding the local availability of key metabolites such as glucose, glutamine, and substrates, such as oxygen from the bone marrow to inflamed tissues. As highlighted in this review, the link between specific metabolic pathways and neutrophil activation has been outlined in many reports. However, the impact of neutrophil activation on metabolic shifts' induction has not yet been explored. Beyond its importance in neutrophil survival capacity in response to available metabolites, metabolic shifts may also contribute to neutrophil population heterogeneity reported in cancer (tumor-associated neutrophil) or auto-immune diseases (Low/High Density Neutrophils). This represents an active field of research. In conclusion, the characterization of neutrophil metabolic shifts is an emerging field that may provide important knowledge on neutrophil physiology and activation modulation. The related question of microenvironmental changes occurring during inflammation, to which neutrophils will respond to, will have to be addressed to fully appreciate the importance of neutrophil metabolic shifts in inflammatory diseases.},

keywords = {energetic metabolism infection inflammation neutrophils nutrient availability oxygen sensing, MARTEYN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}