Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis

Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishm...

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Autores principales:	Tej Pratap Singh, Augusto M. Carvalho, Laís Amorim Sacramento, Elizabeth A. Grice, Phillip Scott
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7ddcb0ee5bb542fc8a2a2376d23e4dcb
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spelling	oai:doaj.org-article:7ddcb0ee5bb542fc8a2a2376d23e4dcb2021-11-11T06:03:59ZMicrobiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis1553-73661553-7374https://doaj.org/article/7ddcb0ee5bb542fc8a2a2376d23e4dcb2021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570469/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells and IL-23. Moreover, experiments using Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses as depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis. Author summary Cutaneous leishmaniasis includes a spectrum of diseases ranging from a single ulcerative lesion to severe metastatic lesions, and the magnitude of the disease is often influenced by factors that are independent from the parasite burden. Here, using L. major infected mice, we discovered that microbiota-dependent IL-17A–secreting ILCs promote increased disease early after infection. While the microbiota driven IL-17A–secreting ILCs mediated inflammatory response was independent of the parasite burden and a type 1 immune responses, it required stimulation of Batf3-dependent skin dendritic cells, production of IL-23 and the presence of neutrophils. This study provides mechanistic insight into how microbiota and the innate immune system influence pathology early after infection with L. major.Tej Pratap SinghAugusto M. CarvalhoLaís Amorim SacramentoElizabeth A. GricePhillip ScottPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Tej Pratap Singh Augusto M. Carvalho Laís Amorim Sacramento Elizabeth A. Grice Phillip Scott Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
description	Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells and IL-23. Moreover, experiments using Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses as depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis. Author summary Cutaneous leishmaniasis includes a spectrum of diseases ranging from a single ulcerative lesion to severe metastatic lesions, and the magnitude of the disease is often influenced by factors that are independent from the parasite burden. Here, using L. major infected mice, we discovered that microbiota-dependent IL-17A–secreting ILCs promote increased disease early after infection. While the microbiota driven IL-17A–secreting ILCs mediated inflammatory response was independent of the parasite burden and a type 1 immune responses, it required stimulation of Batf3-dependent skin dendritic cells, production of IL-23 and the presence of neutrophils. This study provides mechanistic insight into how microbiota and the innate immune system influence pathology early after infection with L. major.
format	article
author	Tej Pratap Singh Augusto M. Carvalho Laís Amorim Sacramento Elizabeth A. Grice Phillip Scott
author_facet	Tej Pratap Singh Augusto M. Carvalho Laís Amorim Sacramento Elizabeth A. Grice Phillip Scott
author_sort	Tej Pratap Singh
title	Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
title_short	Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
title_full	Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
title_fullStr	Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
title_full_unstemmed	Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
title_sort	microbiota instruct il-17a-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/7ddcb0ee5bb542fc8a2a2376d23e4dcb
work_keys_str_mv	AT tejpratapsingh microbiotainstructil17aproducinginnatelymphoidcellstopromoteskininflammationincutaneousleishmaniasis AT augustomcarvalho microbiotainstructil17aproducinginnatelymphoidcellstopromoteskininflammationincutaneousleishmaniasis AT laisamorimsacramento microbiotainstructil17aproducinginnatelymphoidcellstopromoteskininflammationincutaneousleishmaniasis AT elizabethagrice microbiotainstructil17aproducinginnatelymphoidcellstopromoteskininflammationincutaneousleishmaniasis AT phillipscott microbiotainstructil17aproducinginnatelymphoidcellstopromoteskininflammationincutaneousleishmaniasis
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Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis

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