Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.

In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and di...

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Autores principales:	Suresh Pallikkuth, Luca Micci, Zachary S Ende, Robin I Iriele, Barbara Cervasi, Benton Lawson, Colleen S McGary, Kenneth A Rogers, James G Else, Guido Silvestri, Kirk Easley, Jacob D Estes, Francois Villinger, Savita Pahwa, Mirko Paiardini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/469083600eb542f78336284afc46cd6b
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spelling	oai:doaj.org-article:469083600eb542f78336284afc46cd6b2021-11-18T06:05:25ZMaintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.1553-73661553-737410.1371/journal.ppat.1003471https://doaj.org/article/469083600eb542f78336284afc46cd6b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853592/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239) and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i) higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.Suresh PallikkuthLuca MicciZachary S EndeRobin I IrieleBarbara CervasiBenton LawsonColleen S McGaryKenneth A RogersJames G ElseGuido SilvestriKirk EasleyJacob D EstesFrancois VillingerSavita PahwaMirko PaiardiniPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003471 (2013)
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 Suresh Pallikkuth Luca Micci Zachary S Ende Robin I Iriele Barbara Cervasi Benton Lawson Colleen S McGary Kenneth A Rogers James G Else Guido Silvestri Kirk Easley Jacob D Estes Francois Villinger Savita Pahwa Mirko Paiardini Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
description	In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4⁺ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8⁺ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIV(mac239) and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i) higher expression of perforin and granzyme B in total and SIV-specific CD8⁺ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.
format	article
author	Suresh Pallikkuth Luca Micci Zachary S Ende Robin I Iriele Barbara Cervasi Benton Lawson Colleen S McGary Kenneth A Rogers James G Else Guido Silvestri Kirk Easley Jacob D Estes Francois Villinger Savita Pahwa Mirko Paiardini
author_facet	Suresh Pallikkuth Luca Micci Zachary S Ende Robin I Iriele Barbara Cervasi Benton Lawson Colleen S McGary Kenneth A Rogers James G Else Guido Silvestri Kirk Easley Jacob D Estes Francois Villinger Savita Pahwa Mirko Paiardini
author_sort	Suresh Pallikkuth
title	Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
title_short	Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
title_full	Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
title_fullStr	Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
title_full_unstemmed	Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.
title_sort	maintenance of intestinal th17 cells and reduced microbial translocation in siv-infected rhesus macaques treated with interleukin (il)-21.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/469083600eb542f78336284afc46cd6b
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Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21.

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