The Anopheles Mosquito Microbiota and Their Impact on Pathogen Transmission

International audienc

Long-Range Activation of Systemic Immunity through Peptidoglycan Diffusion in Drosophila

The systemic immune response of Drosophila is known to be induced both by septic injury and by oral infection with certain bacteria, and is characterized by the secretion of antimicrobial peptides (AMPs) into the haemolymph. To investigate other possible routes of bacterial infection, we deposited Erwinia carotovora (Ecc15) on various sites of the cuticle and monitored the immune response via expression of the AMP gene Diptericin. A strong response was observed to deposition on the genital plate of males (up to 20% of a septic injury response), but not females. We show that the principal response to genital infection is systemic, but that some AMPs, particularly Defensin, are induced locally in the genital tract. At late time points we detected bacteria in the haemolymph of immune deficient RelishE20 flies, indicating that the genital plate can be a route of entry for pathogens, and that the immune response protects flies against the progression of genital infection. The protective role of the immune response is further illustrated by our observation that RelishE20 flies exhibit significant lethality in response to genital Ecc15 infections. We next show that a systemic immune response can be induced by deposition of the bacterial elicitor peptidoglycan (PGN), or its terminal monomer tracheal cytotoxin (TCT), on the genital plate. This immune response is downregulated by PGRP-LB and Pirk, known regulators of the Imd pathway, and can be suppressed by the overexpression of PGRP-LB in the haemolymph compartment. Finally, we provide strong evidence that TCT can activate a systemic response by crossing epithelia, by showing that radiolabelled TCT deposited on the genital plate can subsequently be detected in the haemolymph. Genital infection is thus an intriguing new model for studying the systemic immune response to local epithelial infections and a potential route of entry for naturally occurring pathogens of Drosophila

A Swiss Army Knife to Cut Malaria Transmission

International audienceThe mosquito microbiota is known to naturally limit malaria transmission, acting directly on parasites and via effects on mosquito immunity and fitness. Using genetically modified bacteria and mosquitoes, two studies uncover new potential of this multipotent prospective tool to reduce disease transmission

Articulations entre réponses locale et systémique dans les défenses antibactériennes de la Drosophile

An immune system protects organisms against infections. During my PhD,I have focused on the local immune responses of Drosophila and on their links with the systemic immune response. The systemic response is induced in the fat body by the presence of bacteria in the body cavity while the local response is initiated when bacteria accumulate within an epithelial tissue. Some local gut infections however have been shown to also induce systemic responses in the absence of bacteria in the body cavity. Thus, a signal from the gut is detected by the fat body. It has been proposed that bacterial peptidoglycan, passing across the gut epithelium, could be this signal. In the first project of my PhD, I characterized a new, genital, mode of infection that induces both a local response of the genital tract and a systemic fat body response. Experiments based on genital deposition of peptidoglycan reveal that this molecule is the signal that passes from the genital tract to the fat body. Preliminary results suggest that its passage requires transcytosis. In my second project, I investigated the function of PGRP-LA. PGRPs are regulators and effectors of the immune response in animals. A transcriptome analysis in larval tracheae suggests that PGRP-LA is involved in the maintenance of a basal level of immune response in healthy conditions. Preliminary results suggest that PGRP-LA is also required for a localised response of the fat body surrounding the salivary glands. These studies provide new insights into the immune responses of the tracheae and genital tract and into the communication between barrier epithelia, specifically the salivary glands and the genital tract, and the fat bodyLe système immunitaire assure le maintien de l'intégrité de l'organisme, luttant notamment contre les infections. Durant ma thèse, j'ai étudié la réponse immunitaire locale et ses liens avec la réponse systémique chez la Drosophile. La réponse systémique, à l'échelle de l'organisme, est induite dans le corps gras en présence de bactéries dans la cavité générale et la réponse locale a lieu en cas d'accumulation de bactéries au contact d'un épithélium. Certaines infections locales, par voie orale, induisent à la fois une réponse locale et une réponse systémique, en absence de bactéries dans la cavité générale : cela implique l'envoi d'un signal au corps gras par l'intestin. Il a été proposé que ce signal serait le peptidoglycane bactérien diffusant à travers l'intestin. Ma thèse est constituée de deux projets. D'une part, j'ai caractérisé un mode d'infection locale, par voie génitale, induisant une réponse locale et systémique. Par dépôt génital de peptidoglycane, j'ai mis en évidence que cette molécule est le signal induisant la réponse systémique. Selon des données préliminaires, elle diffuserait par transcytose. D'autre part, j'ai étudié la fonction de PGRP-LA. Les PGRP sont des régulateurs et des effecteurs de la réponse immunitaire chez les animaux. L'analyse du transcriptome de trachées larvaires suggère que PGRP-LA participe au maintien d'un niveau basal d'immunité locale. Selon des résultats préliminaires, il serait impliqué dans la réponse du corps gras attenant aux glandes salivaires. Ma thèse apporte donc des informations sur la réponse immunitaire dans les trachées et l'appareil génital et sur la communication entre épithélium génital ou salivaire et corps gra

Three new species of Culex (Melanoconion) (Diptera: Culicidae) from French Guiana based on morphological and molecular data

International audienceCulex mosquitoes of the subgenus Melanoconion Theobald, 1903 of the genus Culex Linnaeus, 1758 include numerous species recognized as vectors of viruses affecting humans. This subgenus is the most speciose among the entire mosquito fauna of the Americas. Despite decades of taxonomic research, many species remain undiscovered, especially in the Amazonian biome. In this article, we provide the description of three new species of Culex (Melanoconion) recently discovered in a biological reserve in French Guiana. Culex (Mel.) sallumae n. sp., Cx. (Mel.) hutchingsae n. sp. and Cx. (Mel.) lucakermanni n. sp. are described based on both morphological features of the male genitalia and molecular barcodes obtained from type specimens. Diagnostic characters to assist their identification are provided and their placement within the infrasubgeneric classification of the subgenus Melanoconion is discussed

The tripartite interactions between the mosquito, its microbiota and Plasmodium

Abstract The microbiota of Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity. We also discuss three current challenges in the field, namely the need for a more relevant microbiota composition in experimental mosquitoes involved in vector biology studies, for a better characterisation of the non-bacterial microbiota, and for further functional studies of the microbiota present outside the gut

Le microbiote de moustique et son influence sur la transmission vectorielle

International audienceMosquito microbiota and its influence on disease vectorial transmission. Mosquitoes (Diptera: Culicidae) are found worldwide. Around 100 among 3500 mosquito species are known to be vectors of parasites and viruses, responsible for infectious diseases including malaria and dengue. Mosquitoes host diverse microbial communities that influence disease transmission, either by direct interference or via affecting host immunity and physiology. These microbial communities are present within diverse tissues, including the digestive tract, and vary depending on the sex of the mosquito, its developmental stage, and ecological factors. This review summarizes the current knowledge about the mosquito microbiota, defined as a community of commensal, symbiotic or pathogenic microbes harboured by a host. We first describe the current knowledge on the diversity of the microbiota, that includes bacteria, fungi, parasites and viruses and on its modes of acquisition throughout the mosquito life cycle. We then focus on microbial interactions within the mosquito gut, which notably affect vector competence, and on host-microbe interactions affecting mosquito fitness. Finally, we discuss current or potential methods based on the use of microbes or microbial products to interfere with pathogen transmission or to reduce mosquito lifespan and reproduction.Les moustiques, constituant la famille des Culicidae, sont présents partout dans le monde. Parmi leurs 3500 espèces, on compte une centaine de vecteurs d'agents pathogènes pour l'homme. Ils hébergent des communautés microbiennes qui influencent notamment leur propension à transmettre ces pathogènes par inhibition directe ou en affectant l'immunité et la physiologie de leur hôte. Ces communautés microbiennes colonisent divers tissus, notamment l'appareil digestif, et varient en fonction du sexe, du stade de développement et de facteurs écologiques. Dans cette revue, nous décrivons la diversité du microbiote, incluant des bactéries, des champignons, des parasites et des virus, ainsi que ses modes d'acquisition. Nous faisons état des connaissances sur les interactions microbiennes chez le moustique, qui affectent notamment la compétence vectorielle, et sur l'effet du microbiote sur le moustique. Enfin, nous nous intéressons aux opportunités d'utilisation de microbes ou de dérivés microbiens pour lutter contre la transmission vectorielle. Abstract-Mosquito microbiota and its influence on disease vectorial transmission. Mosquitoes (Diptera: Culicidae) are found worldwide. Around 100 among 3500 mosquito species are known to be vectors of parasites and viruses, responsible for infectious diseases including malaria and dengue. Mosquitoes host diverse microbial communities that influence disease transmission, either by direct interference or via affecting host immunity and physiology. These microbial communities are present within diverse tissues, including the digestive tract, and vary depending on the sex of the mosquito, its developmental stage, and ecological factors. This review summarizes the current knowledge about the mosquito microbiota, defined as a community of commensal, symbiotic or pathogenic microbes harboured by a host. We first describe the current knowledge on the diversity of the microbiota, that includes bacteria, fungi, parasites and viruses and on its modes of acquisition throughout the mosquito life cycle. We then focus on microbial interactions within the mosquito gut, which notably affect vector competence, and on host-microbe interactions affecting mosquito fitness. Finally, we discuss current or potential methods based on the use of microbes or microbial products to interfere with pathogen transmission or to reduce mosquito lifespan and reproduction

Involvement of Microbiota in Insect Physiology: Focus on B Vitamins

International audienceInsects are highly successful in colonizing a wide spectrum of ecological niches and in feeding on a wide diversity of diets. This is notably linked to their capacity to get from their microbiota any essential component lacking in the diet such as vitamins and amino acids. Over a century of research based on dietary analysis, antimicrobial treatment, gnotobiotic rearing, and culture-independent microbe detection progressively generated a wealth of information about the roleof the microbiota in specific aspects of insect fitness. Thanks to the recent increase in sequencing capacities, whole-genome sequencing of a number of symbionts has facilitated tracing of biosynthesis pathways, validation of experimental data and evolutionary analyses. This field of research has generated a considerable set of data in a diversity of hosts harboring specific symbionts or nonspecific microbiota members. Here, we review the current knowledge on the involvement of the microbiota in insect and tick nutrition, with a particular focus on B vitamin provision. We specifically question if there is any specificity of B vitamin provision by symbiontscompared to the redundant yet essential contribution of nonspecific microbes. We successively highlight the known aspects of microbial vitamin provision during three main life stages of invertebrates: postembryonic development, adulthood, and reproduction