IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine...

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Main Authors: Abenaya Muralidharan, Md Bashir Uddin, Christopher Bauer, Wenzhe Wu, Xiaoyong Bao, Keer Sun
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/1/147
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author Abenaya Muralidharan
Md Bashir Uddin
Christopher Bauer
Wenzhe Wu
Xiaoyong Bao
Keer Sun
author_facet Abenaya Muralidharan
Md Bashir Uddin
Christopher Bauer
Wenzhe Wu
Xiaoyong Bao
Keer Sun
author_sort Abenaya Muralidharan
collection DOAJ
description The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary <i>Streptococcus pneumoniae</i> infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic <i>Ifng<sup>−/−</sup></i> mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic <i>Ifng<sup>−/−</sup></i> mice in the absence of RSV infection. Furthermore, neither WT nor <i>Ifng<sup>−/−</sup></i> mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.
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spelling doaj.art-a56ced5a5dfc480fbcada91e78594df12023-11-23T15:43:04ZengMDPI AGViruses1999-49152022-01-0114114710.3390/v14010147IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult MiceAbenaya Muralidharan0Md Bashir Uddin1Christopher Bauer2Wenzhe Wu3Xiaoyong Bao4Keer Sun5Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1017, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USADepartment of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555-0372, USADepartment of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555-0372, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USAThe susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary <i>Streptococcus pneumoniae</i> infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic <i>Ifng<sup>−/−</sup></i> mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic <i>Ifng<sup>−/−</sup></i> mice in the absence of RSV infection. Furthermore, neither WT nor <i>Ifng<sup>−/−</sup></i> mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.https://www.mdpi.com/1999-4915/14/1/147RSVasthmacomorbidity
spellingShingle Abenaya Muralidharan
Md Bashir Uddin
Christopher Bauer
Wenzhe Wu
Xiaoyong Bao
Keer Sun
IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
Viruses
RSV
asthma
comorbidity
title IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
title_full IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
title_fullStr IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
title_full_unstemmed IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
title_short IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice
title_sort ifn γ attenuates eosinophilic inflammation but is not essential for protection against rsv enhanced asthmatic comorbidity in adult mice
topic RSV
asthma
comorbidity
url https://www.mdpi.com/1999-4915/14/1/147
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