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Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A

The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleu...

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Autores principales: Xue, Chunxue, Wen, Mingjie, Bao, Linlin, Li, Hui, Li, Fengdi, Liu, Meng, Lv, Qi, An, Yunqing, Zhang, Xulong, Cao, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583159/
https://www.ncbi.nlm.nih.gov/pubmed/28912779
http://dx.doi.org/10.3389/fimmu.2017.01054
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author Xue, Chunxue
Wen, Mingjie
Bao, Linlin
Li, Hui
Li, Fengdi
Liu, Meng
Lv, Qi
An, Yunqing
Zhang, Xulong
Cao, Bin
author_facet Xue, Chunxue
Wen, Mingjie
Bao, Linlin
Li, Hui
Li, Fengdi
Liu, Meng
Lv, Qi
An, Yunqing
Zhang, Xulong
Cao, Bin
author_sort Xue, Chunxue
collection PubMed
description The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1) pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4(+)Th and CD8(+)Tc cells, gradually increased and peaked at 3 days post-infection (dpi). Further analysis revealed that the Vγ4(+)γδT subset, but not the Vγ1(+)γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF) and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4(+)γδT subset), but not CD4(+)Th and CD8(+)Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN)-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D), and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4(+)γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4(+)γδT cells, at least, in part mediated influenza A (H1N1) pdm09-induced immunopathological injury. This mechanism might serve as a promising new target for the prevention and treatment of ALI induced by influenza A (H1N1) pdm09.
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spelling pubmed-55831592017-09-14 Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A Xue, Chunxue Wen, Mingjie Bao, Linlin Li, Hui Li, Fengdi Liu, Meng Lv, Qi An, Yunqing Zhang, Xulong Cao, Bin Front Immunol Immunology The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1) pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4(+)Th and CD8(+)Tc cells, gradually increased and peaked at 3 days post-infection (dpi). Further analysis revealed that the Vγ4(+)γδT subset, but not the Vγ1(+)γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF) and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4(+)γδT subset), but not CD4(+)Th and CD8(+)Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN)-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D), and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4(+)γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4(+)γδT cells, at least, in part mediated influenza A (H1N1) pdm09-induced immunopathological injury. This mechanism might serve as a promising new target for the prevention and treatment of ALI induced by influenza A (H1N1) pdm09. Frontiers Media S.A. 2017-08-31 /pmc/articles/PMC5583159/ /pubmed/28912779 http://dx.doi.org/10.3389/fimmu.2017.01054 Text en Copyright © 2017 Xue, Wen, Bao, Li, Li, Liu, Lv, An, Zhang and Cao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Xue, Chunxue
Wen, Mingjie
Bao, Linlin
Li, Hui
Li, Fengdi
Liu, Meng
Lv, Qi
An, Yunqing
Zhang, Xulong
Cao, Bin
Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title_full Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title_fullStr Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title_full_unstemmed Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title_short Vγ4(+)γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
title_sort vγ4(+)γδt cells aggravate severe h1n1 influenza virus infection-induced acute pulmonary immunopathological injury via secreting interleukin-17a
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583159/
https://www.ncbi.nlm.nih.gov/pubmed/28912779
http://dx.doi.org/10.3389/fimmu.2017.01054
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