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Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging

ABSTRACT: Lung tissue-resident memory CD8+ T-cells (Trm) are critical for heterosubtypic immunity against influenza virus-(IAV)-reinfection. How these cells surveil the lung, respond to infection and interact with other cells remains unresolved. Here, we used mouse models to identify and enrich lung Trm in combination with intravital and static imaging to assess spatiotemporal dynamics of IAV-induced lung TRM before and after recall-infection. CD69+CD103+ Trm localize to sites of prior influenza infection where they exhibit substantially slower movement properties than non-Trm that also surveil the lung. After rechallenge, lung Trm form tight clusters in an antigen-dependent manner. IAV-specific Trm express several factors that regulate myeloid cell biology and their protective immune responses are accompanied by activation and migration of dendritic cells to draining lymph nodes and recruitment of inflammatory monocytes. Overall, these data reveal the dynamic landscapes of lung Trm cells associated with early protective immunity against IAV infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE242558 | GEO | 2024/07/22

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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Dynamic landscapes and protective immunity coordinated by influenza-specific lung-resident memory CD8+ T cells revealed by intravital imaging

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