Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies
Allergic (Th2high immunophenotype) asthmatics have a heightened susceptibility to common respiratory viral infections such as human rhinovirus. Evidence suggests that the innate interferon response is deficient in asthmatic/atopic individuals, while other studies show no differences in antiviral res...
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doaj-237ed14507ad469c8d771423e2cedce82020-11-24T22:01:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01805387618Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model StudiesJean-François Lauzon-Joset0Anya C. Jones1Anya C. Jones2Kyle T. Mincham3Kyle T. Mincham4Jenny A. Thomas5Louis A. Rosenthal6Anthony Bosco7Patrick G. Holt8Deborah H. Strickland9Telethon Kids Institute, University of Western Australia, Perth, WA, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaSchool of Medicine, University of Western Australia, Perth, WA, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaSchool of Medicine, University of Western Australia, Perth, WA, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United StatesTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaTelethon Kids Institute, University of Western Australia, Perth, WA, AustraliaAllergic (Th2high immunophenotype) asthmatics have a heightened susceptibility to common respiratory viral infections such as human rhinovirus. Evidence suggests that the innate interferon response is deficient in asthmatic/atopic individuals, while other studies show no differences in antiviral response pathways. Unsensitized and OVA-sensitized/challenged Th2high (BN rats) and Th2low immunophenotype (PVG rats) animals were inoculated intranasally with attenuated mengovirus (vMC0). Sensitized animals were exposed/unexposed during the acute viral response phase. Cellular and transcriptomic profiling was performed on bronchoalveolar lavage cells. In unsensitized PVG rats, vMC0 elicits a prototypical antiviral response (neutrophilic airways inflammation, upregulation of Th1/type I interferon-related pathways). In contrast, response to infection in the Th2high BN rats was associated with a radically altered intrinsic host response to respiratory viral infection, characterized by macrophage influx/Th2-associated pathways. In sensitized animals, response to virus infection alone was not altered compared to unsensitized animals. However, allergen exposure of sensitized animals during viral infection unleashes a notably exaggerated airways inflammatory response profile orders of magnitude higher in BN versus PVG rats despite similar viral loads. The co-exposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures. Similar factors may underlie the hyper-susceptibility to infection-associated airways inflammation characteristic of the human Th2high immunophenotype.https://www.frontiersin.org/article/10.3389/fimmu.2018.01805/fullrhinovirusTh2-atopytype I interferonallergic asthmamicroarray |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jean-François Lauzon-Joset Anya C. Jones Anya C. Jones Kyle T. Mincham Kyle T. Mincham Jenny A. Thomas Louis A. Rosenthal Anthony Bosco Patrick G. Holt Deborah H. Strickland |
spellingShingle |
Jean-François Lauzon-Joset Anya C. Jones Anya C. Jones Kyle T. Mincham Kyle T. Mincham Jenny A. Thomas Louis A. Rosenthal Anthony Bosco Patrick G. Holt Deborah H. Strickland Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies Frontiers in Immunology rhinovirus Th2-atopy type I interferon allergic asthma microarray |
author_facet |
Jean-François Lauzon-Joset Anya C. Jones Anya C. Jones Kyle T. Mincham Kyle T. Mincham Jenny A. Thomas Louis A. Rosenthal Anthony Bosco Patrick G. Holt Deborah H. Strickland |
author_sort |
Jean-François Lauzon-Joset |
title |
Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies |
title_short |
Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies |
title_full |
Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies |
title_fullStr |
Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies |
title_full_unstemmed |
Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies |
title_sort |
atopy-dependent and independent immune responses in the heightened severity of atopics to respiratory viral infections: rat model studies |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-08-01 |
description |
Allergic (Th2high immunophenotype) asthmatics have a heightened susceptibility to common respiratory viral infections such as human rhinovirus. Evidence suggests that the innate interferon response is deficient in asthmatic/atopic individuals, while other studies show no differences in antiviral response pathways. Unsensitized and OVA-sensitized/challenged Th2high (BN rats) and Th2low immunophenotype (PVG rats) animals were inoculated intranasally with attenuated mengovirus (vMC0). Sensitized animals were exposed/unexposed during the acute viral response phase. Cellular and transcriptomic profiling was performed on bronchoalveolar lavage cells. In unsensitized PVG rats, vMC0 elicits a prototypical antiviral response (neutrophilic airways inflammation, upregulation of Th1/type I interferon-related pathways). In contrast, response to infection in the Th2high BN rats was associated with a radically altered intrinsic host response to respiratory viral infection, characterized by macrophage influx/Th2-associated pathways. In sensitized animals, response to virus infection alone was not altered compared to unsensitized animals. However, allergen exposure of sensitized animals during viral infection unleashes a notably exaggerated airways inflammatory response profile orders of magnitude higher in BN versus PVG rats despite similar viral loads. The co-exposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures. Similar factors may underlie the hyper-susceptibility to infection-associated airways inflammation characteristic of the human Th2high immunophenotype. |
topic |
rhinovirus Th2-atopy type I interferon allergic asthma microarray |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01805/full |
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