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Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium
Although asthmatics has been considered to be highly susceptible to respiratory viral infection and most studies have focused on exacerbation of asthma by influenza A virus (IAV) infection, few experimental evidences exist to directly demonstrate that asthmatic mice are actually resistant to IAV inf...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966536/ https://www.ncbi.nlm.nih.gov/pubmed/29867963 http://dx.doi.org/10.3389/fimmu.2018.00986 |
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author | An, Sujin Jeon, Yung Jin Jo, Ara Lim, Hyun Jung Han, Young Eun Cho, Sung Woo Kim, Hye Young Kim, Hyun Jik |
author_facet | An, Sujin Jeon, Yung Jin Jo, Ara Lim, Hyun Jung Han, Young Eun Cho, Sung Woo Kim, Hye Young Kim, Hyun Jik |
author_sort | An, Sujin |
collection | PubMed |
description | Although asthmatics has been considered to be highly susceptible to respiratory viral infection and most studies have focused on exacerbation of asthma by influenza A virus (IAV) infection, few experimental evidences exist to directly demonstrate that asthmatic mice are actually resistant to IAV infection. Here, we show that asthmatic mice are not highly susceptible to IAV in the early stage of infection and type III interferon (IFN) maintains antiviral immune response in the lung of IAV-infected asthmatic mouse resulting in inhibition of initial viral spread. C57BL/6 mice with allergic asthma were infected with IAV (WS/33: H1N1) and survival rate, body weight, viral titer, histopathological findings of lung and cytokine profiles including IFNs and Th2 cytokines were measured. Notably, asthmatic mice were significantly resistant to IAV and showed lower viral load until 7 days after infection. Furthermore, IAV-infected asthmatic mice exhibited decreased Th2-related inflammation in lung tissue until 7 days. These increased antiviral resistant mechanism and reduced Th2 inflammation were attributable to rapid induction of type III IFNs and blockade of type III IFNs in asthmatic lung led to aggravated IAV infection and to enhance the production of Th2 cytokines. Asthmatic mice showed bi-phasic responses against IAV-caused lung infection such as rapid production of type III IFNs and subsequent induction of type II IFNs. Actually, IAV-infected asthmatic mice become vulnerable to IAV infection after 7 days with noticeable morbidity and severe weight loss. However, intranasal administration of type III IFNs protects completely asthmatic mice from IAV-mediated immunopathology and lung infection until 14 days after infection. Taken together, our study indicates that the rapid induction of type III IFN might be distinctive immunological findings in the respiratory tract of IAV-infected asthmatic mice at the early stage of infection and crucial for suppression of initial viral spread in vivo asthma accompanying with restriction of Th2 cytokine productions. |
format | Online Article Text |
id | pubmed-5966536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59665362018-06-04 Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium An, Sujin Jeon, Yung Jin Jo, Ara Lim, Hyun Jung Han, Young Eun Cho, Sung Woo Kim, Hye Young Kim, Hyun Jik Front Immunol Immunology Although asthmatics has been considered to be highly susceptible to respiratory viral infection and most studies have focused on exacerbation of asthma by influenza A virus (IAV) infection, few experimental evidences exist to directly demonstrate that asthmatic mice are actually resistant to IAV infection. Here, we show that asthmatic mice are not highly susceptible to IAV in the early stage of infection and type III interferon (IFN) maintains antiviral immune response in the lung of IAV-infected asthmatic mouse resulting in inhibition of initial viral spread. C57BL/6 mice with allergic asthma were infected with IAV (WS/33: H1N1) and survival rate, body weight, viral titer, histopathological findings of lung and cytokine profiles including IFNs and Th2 cytokines were measured. Notably, asthmatic mice were significantly resistant to IAV and showed lower viral load until 7 days after infection. Furthermore, IAV-infected asthmatic mice exhibited decreased Th2-related inflammation in lung tissue until 7 days. These increased antiviral resistant mechanism and reduced Th2 inflammation were attributable to rapid induction of type III IFNs and blockade of type III IFNs in asthmatic lung led to aggravated IAV infection and to enhance the production of Th2 cytokines. Asthmatic mice showed bi-phasic responses against IAV-caused lung infection such as rapid production of type III IFNs and subsequent induction of type II IFNs. Actually, IAV-infected asthmatic mice become vulnerable to IAV infection after 7 days with noticeable morbidity and severe weight loss. However, intranasal administration of type III IFNs protects completely asthmatic mice from IAV-mediated immunopathology and lung infection until 14 days after infection. Taken together, our study indicates that the rapid induction of type III IFN might be distinctive immunological findings in the respiratory tract of IAV-infected asthmatic mice at the early stage of infection and crucial for suppression of initial viral spread in vivo asthma accompanying with restriction of Th2 cytokine productions. Frontiers Media S.A. 2018-05-17 /pmc/articles/PMC5966536/ /pubmed/29867963 http://dx.doi.org/10.3389/fimmu.2018.00986 Text en Copyright © 2018 An, Jeon, Jo, Lim, Han, Cho, Kim and Kim. https://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) and the copyright owner 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 An, Sujin Jeon, Yung Jin Jo, Ara Lim, Hyun Jung Han, Young Eun Cho, Sung Woo Kim, Hye Young Kim, Hyun Jik Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title | Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title_full | Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title_fullStr | Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title_full_unstemmed | Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title_short | Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium |
title_sort | initial influenza virus replication can be limited in allergic asthma through rapid induction of type iii interferons in respiratory epithelium |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966536/ https://www.ncbi.nlm.nih.gov/pubmed/29867963 http://dx.doi.org/10.3389/fimmu.2018.00986 |
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