Insect Gut Microbiota: Accessories to the Bite
2018; Cell Press; Volume: 23; Issue: 1 Linguagem: Inglês
10.1016/j.chom.2017.12.016
ISSN1934-6069
Autores Tópico(s)Research on Leishmaniasis Studies
ResumoThe Leishmania parasite is transmitted via the bite of a sand fly. In this issue of Cell Host & Microbe, Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar report that sand fly gut microbiota are also transferred to the bite site, promoting neutrophil recruitment and parasite dissemination to distal organs. The Leishmania parasite is transmitted via the bite of a sand fly. In this issue of Cell Host & Microbe, Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar report that sand fly gut microbiota are also transferred to the bite site, promoting neutrophil recruitment and parasite dissemination to distal organs. The majority of pathogens transmitted to their mammalian hosts by arthropod vectors are inoculated into the bite site along with saliva during blood feeding. Delivery of pathogens via a blood-feeding vector differs in its infection outcome compared to when pathogens are introduced into the skin with a needle and syringe. The dynamic of this tripartite interaction at the bite site—insect saliva-pathogen-mammalian responses—is complex. Many studies have addressed the components of saliva that promote infections in ways that differ from a needle challenge. Saliva contains a variety of biochemicals, including anticoagulants, vasodilators, anesthetics, and immunomodulators, which enable arthropods to mitigate host vasoconstriction, coagulation, and immune responsiveness (Abdeladhim et al., 2014Abdeladhim M. Kamhawi S. Valenzuela J.G. What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.Infect. Genet. Evol. 2014; 28: 691-703Crossref PubMed Scopus (100) Google Scholar, Liu and Bonnet, 2014Liu X.Y. Bonnet S.I. Hard tick factors implicated in pathogen transmission.PLoS Negl. Trop. Dis. 2014; 8: e2566Crossref PubMed Scopus (61) Google Scholar). Additionally, pathogens colonizing the salivary glands of vector arthropods can influence the composition of saliva in ways that prolong the survival of the parasites at the bite site and promote pathogen dissemination and disease severity (Van Den Abbeele et al., 2010Van Den Abbeele J. Caljon G. De Ridder K. De Baetselier P. Coosemans M. Trypanosoma brucei modifies the tsetse salivary composition, altering the fly feeding behavior that favors parasite transmission.PLoS Pathog. 2010; 6: e1000926Crossref PubMed Scopus (81) Google Scholar). Finally, parasites can actively manipulate immune responses at the bite site by secreting molecules, such as proteophosphoglycans (Rogers, 2012Rogers M.E. The role of leishmania proteophosphoglycans in sand fly transmission and infection of the Mammalian host.Front. Microbiol. 2012; 3: 223Crossref PubMed Scopus (70) Google Scholar), or through the factors contained within parasite-produced exosomes introduced into the bite site in saliva (Atayde et al., 2015Atayde V.D. Aslan H. Townsend S. Hassani K. Kamhawi S. Olivier M. Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut.Cell Rep. 2015; 13: 957-967Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar). In a new paper in this issue of Cell Host & Microbe, Ranadhir Dey and colleagues have expanded the list of bioactive saliva-associated compounds to include the vector's commensal gut microbiota (Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar). Microbial fauna associated with adult insects impacts various important physiologies, influencing nutritional and immune system status as well as reproductive fitness. Characterization of the insect gut microbiota has revealed a highly diverse community of organisms composed of environmentally acquired microbes and/or maternally transmitted symbiotic fauna. In some insects, the gut is dominated by obligate endosymbionts, which provision their hosts with micronutrients that are lacking from their restricted diets. This metabolic complementation enables insects, such as aphids, weevils, and tsetse flies, to survive and reproduce on nutritionally limited diets. Other vertically transmitted microbes, such as Wolbachia, can manipulate their hosts' reproductive physiology in ways that benefit and enable the spread of infected hosts over those that are Wolbachia naive in nature. The microbiota residing in the insect gut can also stimulate the vector's immune system, rendering the insect hosts more resistant to infection with pathogens—a mutually beneficial trait that exludes competition between the microbial fauna. Endosymbionts have been shown to confer resistance to their hosts against parasites and viruses; for example, gut microbes protect bumble bees from intestinal parasites (Koch and Schmid-Hempel, 2011Koch H. Schmid-Hempel P. Socially transmitted gut microbiota protect bumble bees against an intestinal parasite.Proc. Natl. Acad. Sci. USA. 2011; 108: 19288-19292Crossref PubMed Scopus (505) Google Scholar, Moreira et al., 2009Moreira L.A. Iturbe-Ormaetxe I. Jeffery J.A. Lu G. Pyke A.T. Hedges L.M. Rocha B.C. Hall-Mendelin S. Day A. Riegler M. et al.A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium.Cell. 2009; 139: 1268-1278Abstract Full Text Full Text PDF PubMed Scopus (1078) Google Scholar) and the obligate endosymbiont of tsetse, Wigglesworthia, indirectly provides protection against trypanosomes (Wang and Aksoy, 2012Wang J. Aksoy S. PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse's offspring.Proc. Natl. Acad. Sci. USA. 2012; 109: 10552-10557Crossref PubMed Scopus (71) Google Scholar). Now, Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar document yet another important role for the commensal gut microbiota that goes beyond their influence on their insect host physiology—this time promoting pathogen survival and dissemination in the mammalian host. Leishmania parasites are transmitted by bite of phlebotomine sand flies. This study focuses on the transmission process of Leishmania donavani, which causes a visceral disease with high fatality in untreated patients. Following the sand fly bite, neutrophils are recruited to the bite site in response to tissue damage due to insect probing. Sustained recruitment of neutrophils and neutrophil-driven inflammation are essential for Leishmania survival and migration from the skin to the liver and spleen. In fact, the role of neutrophils in the pathogen transmission process at the bite site appears to be a conserved mechanism in insect-transmitted pathogens. A similar increased recruitment of neutrophils following bites by virus-infected mosquitoes was also shown to enhance viral establishment and dissemination due to the enriched number of virus-susceptible myeloid cells arriving at the bite site (Pingen et al., 2016Pingen M. Bryden S.R. Pondeville E. Schnettler E. Kohl A. Merits A. Fazakerley J.K. Graham G.J. McKimmie C.S. Host inflammatory response to mosquito bites enhances the severity of arbovirus infection.Immunity. 2016; 44: 1455-1469Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar). Here, Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar address the mechanism(s) that drive the sustained recruitment of neutrophils following sand fly feeding. Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar compare the host bite site immune responses using Leishmania-infected and uninfected sand fly bites, as well as cultured infective parasites needle inoculated with and without sand fly salivary gland extracts. Their findings confirm that persistent neutrophil, as well as degranulated mast cell recruitment, occurs only through the natural fly bite, albeit the recruitment of immune cells is higher in tissues that receive an infectious fly bite. Of significance, high induction of levels of the cytokine IL1β, as well as induction of TNFα, NOS2, and IFNγ, supports the fact that fly bites activate an inflammatory response at the bite site in sand fly-challenged mice. They also confirm higher levels of the IL1β protein produced by the significantly higher numbers of neutrophils in tissue lysates from infected bites. Levels of NLRP3, pro-caspase, and cleaved caspase were also consistently higher at sites that received infected fly bites, suggesting that this particular stimulus results in a more efficient assembly of the inflammasome. Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar further demonstrate that Leishmania parasites activate the inflammasome in bone-marrow-derived macrophages (BMDMs) if the cells were lipopolysaccharide (LPS) primed, and high levels of mature IL1β were only produced in these cells in the presence of LPS. Collectively, these findings confirm the formation of an inflammasome structure in a natural fly bite and a role for LPS in its formation in vitro. Next, Dey et al., 2018Dey R. Joshi A.B. Oliveira F. Pereira L. Guimarães-Costa A.B. Serafim T.D. de Castro W. Coutinho-Abreu I.V. Bhattacharya P. Townsend S. et al.Microbes egested during bites of infected sand flies augment severity of Leishmaniasis via inflammasome-derived IL-1β.Cell Host Microbe. 2018; 23 (this issue): 134-143Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar queried whether LPS could play a role in priming inflammasome formation during the natural transmission process and what the source of the LPS at the bite site could be. In a set of elegant experiments to address these questions, they show that the source of the LPS is the midgut microbiota, which is regurgitated into the bite site during feeding. Sand flies treated with antibiotics to reduce the microbiota are not compromised for Leishmania infection development in the sand fly vector. However, microbiota-free Leishmania-infected sand fly bites are impaired in inflammasome assembly, as noted by reduced quantities of IL1β, NLRP3, pro-caspase 1, and cleaved caspase1. Finally, interference with inflammasome assembly processes, as well as introduction of parasites via the bite of microbiota-cured infected flies, all reduce parasite dissemination from the skin to the spleen. Interestingly, the success of disease progression could be only partially rescued when intradermal infections are supplemented with a cultured sand fly gut microbe or with LPS, indicating that additional components of the infectious inoculum are necessary to get the full impact of the infected fly bite. Commensal microbes perform several important functions within their vector hosts that largely benefit the insects, while the microbes themselves receive protection and ample nutrients in a protective niche. This work documents yet an additional role for insect microbiota, which is the facilitation of parasite transmission and infection establishment processes in the mammalian host. The study also extends our knowledge of the biological components present in the infectious inoculum that influence disease outcome at the bite site. Besides the gut tissue, commensal microbes also inhabit the salivary glands of important vectors, such as ticks, mosquitoes, and tsetse flies. Thus, their potential introduction via saliva to the bite site during blood feeding further signifies their potential role in pathogen transmission processes in multiple disease systems. Given that the microbiota composition could vary between parasite-infected and uninfected vectors, it remains to be determined whether further commensal microbiota complexities and unique pathogen-microbiota combinations may be differentially driving the transmission success of parasites in the mammalian host. Gut Microbes Egested during Bites of Infected Sand Flies Augment Severity of Leishmaniasis via Inflammasome-Derived IL-1βDey et al.Cell Host & MicrobeDecember 28, 2017In BriefNeutrophils recruited to sand fly bite sites shelter Leishmania, augmenting disease. Dey et al. demonstrate that egestion of sand fly gut microbes into host skin primes the inflammasome to produce IL-1β, which sustains neutrophil recruitment. Removing gut microbiota or blocking IL-1β before transmission abolishes neutrophil recruitment and impairs Leishmania dissemination. Full-Text PDF Open Archive
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