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ORAI1 is required for T cell mediated allergic airway inflammation but not antiviral immunity in the lung

ABSTRACT: This study investigates the role of store-operated calcium entry (SOCE) in T cell-mediated immune responses to pulmonary influenza A virus (IAV) infection and allergic airway inflammation after immunization by house dust mite (HDM) allergens. We conducted a comparative gene expression analysis of antigen-specific CD4+ T cells from wildtype (WT) and Orai1fl/fl Cd4Cre mice that were adoptively transferred to TCRalpha knockout mice followed by sensitization / challenge with HDM or infection with influenza A virus (IAV) strain x31. Donor CD4+ T cells were isolated from the lungs of host mice at days 9 (IAV) and 14 (HDM), RNA was isolated and processed for bulk RNA sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE184228 | GEO | 2022/05/01

REPOSITORIES: GEO

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Project description:Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection This model is described in the article: Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. J. Virol. 2010 Jul; 84(13): 6687-6698 Abstract: Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is approximately 1.2 days, and the half-life of free infectious IAV is approximately 4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is approximately 0.5 days, and the average half-life of free infectious virus is approximately 1.8 min. During the adaptive phase, model fitting confirms that CD8(+) CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. This model is hosted on BioModels Database and identified by: BIOMD0000000546. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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ORAI1 is required for T cell mediated allergic airway inflammation but not antiviral immunity in the lung

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