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Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome
Most West Nile virus (WNV) infections are asymptomatic, but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death. Evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection. However, other...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721872/ https://www.ncbi.nlm.nih.gov/pubmed/26795118 http://dx.doi.org/10.1371/journal.ppat.1005375 |
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author | James, Eddie A. Gates, Theresa J. LaFond, Rebecca E. Yamamoto, Shinobu Ni, Chester Mai, Duy Gersuk, Vivian H. O’Brien, Kimberly Nguyen, Quynh-Anh Zeitner, Brad Lanteri, Marion C. Norris, Philip J. Chaussabel, Damien Malhotra, Uma Kwok, William W. |
author_facet | James, Eddie A. Gates, Theresa J. LaFond, Rebecca E. Yamamoto, Shinobu Ni, Chester Mai, Duy Gersuk, Vivian H. O’Brien, Kimberly Nguyen, Quynh-Anh Zeitner, Brad Lanteri, Marion C. Norris, Philip J. Chaussabel, Damien Malhotra, Uma Kwok, William W. |
author_sort | James, Eddie A. |
collection | PubMed |
description | Most West Nile virus (WNV) infections are asymptomatic, but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death. Evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection. However, other data suggest that neurologic symptoms may arise as a consequence of immune mediated damage. We demonstrate that elevated immune responses are present in neuroinvasive disease by directly characterizing WNV-specific T cells in subjects with laboratory documented infections using human histocompatibility leukocyte antigen (HLA) class II tetramers. Subjects with neuroinvasive infections had higher overall numbers of WNV-specific T cells than those with asymptomatic infections. Independent of this, we also observed age related increases in WNV-specific T cell responses. Further analysis revealed that WNV-specific T cell responses included a population of atypically polarized CXCR3+CCR4+CCR6- T cells, whose presence was highly correlated with neuroinvasive disease. Moreover, a higher proportion of WNV-specific T cells in these subjects co-produced interferon-γ and interleukin 4 than those from asymptomatic subjects. More globally, subjects with neuroinvasive infections had reduced numbers of CD4+FoxP3+ Tregs that were CTLA4 positive and exhibited a distinct upregulated transcript profile that was absent in subjects with asymptomatic infections. Thus, subjects with neuroinvasive WNV infections exhibited elevated, dysregulated, and atypically polarized responses, suggesting that immune mediated damage may indeed contribute to pathogenic outcomes. |
format | Online Article Text |
id | pubmed-4721872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47218722016-01-30 Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome James, Eddie A. Gates, Theresa J. LaFond, Rebecca E. Yamamoto, Shinobu Ni, Chester Mai, Duy Gersuk, Vivian H. O’Brien, Kimberly Nguyen, Quynh-Anh Zeitner, Brad Lanteri, Marion C. Norris, Philip J. Chaussabel, Damien Malhotra, Uma Kwok, William W. PLoS Pathog Research Article Most West Nile virus (WNV) infections are asymptomatic, but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death. Evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection. However, other data suggest that neurologic symptoms may arise as a consequence of immune mediated damage. We demonstrate that elevated immune responses are present in neuroinvasive disease by directly characterizing WNV-specific T cells in subjects with laboratory documented infections using human histocompatibility leukocyte antigen (HLA) class II tetramers. Subjects with neuroinvasive infections had higher overall numbers of WNV-specific T cells than those with asymptomatic infections. Independent of this, we also observed age related increases in WNV-specific T cell responses. Further analysis revealed that WNV-specific T cell responses included a population of atypically polarized CXCR3+CCR4+CCR6- T cells, whose presence was highly correlated with neuroinvasive disease. Moreover, a higher proportion of WNV-specific T cells in these subjects co-produced interferon-γ and interleukin 4 than those from asymptomatic subjects. More globally, subjects with neuroinvasive infections had reduced numbers of CD4+FoxP3+ Tregs that were CTLA4 positive and exhibited a distinct upregulated transcript profile that was absent in subjects with asymptomatic infections. Thus, subjects with neuroinvasive WNV infections exhibited elevated, dysregulated, and atypically polarized responses, suggesting that immune mediated damage may indeed contribute to pathogenic outcomes. Public Library of Science 2016-01-21 /pmc/articles/PMC4721872/ /pubmed/26795118 http://dx.doi.org/10.1371/journal.ppat.1005375 Text en © 2016 James et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article James, Eddie A. Gates, Theresa J. LaFond, Rebecca E. Yamamoto, Shinobu Ni, Chester Mai, Duy Gersuk, Vivian H. O’Brien, Kimberly Nguyen, Quynh-Anh Zeitner, Brad Lanteri, Marion C. Norris, Philip J. Chaussabel, Damien Malhotra, Uma Kwok, William W. Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title | Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title_full | Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title_fullStr | Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title_full_unstemmed | Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title_short | Neuroinvasive West Nile Infection Elicits Elevated and Atypically Polarized T Cell Responses That Promote a Pathogenic Outcome |
title_sort | neuroinvasive west nile infection elicits elevated and atypically polarized t cell responses that promote a pathogenic outcome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721872/ https://www.ncbi.nlm.nih.gov/pubmed/26795118 http://dx.doi.org/10.1371/journal.ppat.1005375 |
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