Chronic Ethanol Consumption Reduces Existing CD8 T Cell Memory and Is Associated with Lesions in Protection against Secondary Influenza A Virus Infections

Zeb R Zacharias; Kevin L Legge

doi:10.4049/jimmunol.1900770

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Chronic Ethanol Consumption Reduces Existing CD8 T Cell Memory and Is Associated with Lesions in Protection against Secondary Influenza A Virus Infections

Journal article

Peer reviewed

Chronic Ethanol Consumption Reduces Existing CD8 T Cell Memory and Is Associated with Lesions in Protection against Secondary Influenza A Virus Infections

Zeb R Zacharias and Kevin L Legge

The Journal of immunology (1950), Vol.203(12), pp.3313-3324

12/15/2019

DOI: 10.4049/jimmunol.1900770

PMCID: PMC6904436

PMID: 31712384

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Abstract

Chronic alcohol consumption is associated with an increased incidence of disease severity during pulmonary infections. Our previous work in a mouse model of chronic alcohol consumption has detailed that the primary influenza A virus (IAV)-specific CD8 T cell response in mice that consumed ethanol (EtOH) had a reduced proliferative capacity as well as the ability to kill IAV target cells. Interestingly, recent studies have highlighted that human alcoholics have an increased susceptibility to IAV infections, even though they likely possess pre-existing immunity to IAV. However, the effects of chronic alcohol consumption on pre-existing immune responses (i.e., memory) to IAV have not been explored. Our results presented in this study show that IAV-immune mice that then chronically consumed alcohol (X31→EtOH) exhibited increased morbidity and mortality following IAV re-exposure compared with IAV-immune mice that had consumed water (X31→H O). This increased susceptibility in X31→EtOH mice was associated with reduced IAV-specific killing of target cells and a reduction in the number of IAV-specific CD8 T cells within the lungs. Furthermore, upon IAV challenge, recruitment of the remaining memory IAV-specific CD8 T cells into the lungs is reduced in X31→EtOH mice. This altered recruitment is associated with a reduced pulmonary expression of CXCL10 and CXCL11, which are chemokines that are important for T cell recruitment to the lungs. Overall, these results demonstrate that chronic alcohol consumption negatively affects the resting memory CD8 T cell response and reduces the ability of memory T cells to be recruited to the site of infection upon subsequent exposures, therein contributing to an enhanced susceptibility to IAV infections.

Alcoholic Beverages - adverse effects

Animals

CD8-Positive T-Lymphocytes - immunology

Chemokine CXCL10 - metabolism

Chemokine CXCL11 - metabolism

Disease Susceptibility - chemically induced

Ethanol - administration & dosage

Ethanol - pharmacology

Immunologic Memory - drug effects

Influenza A virus

Lung - drug effects

Lung - immunology

Mice

Mice, Inbred C57BL

Mice, Transgenic

Orthomyxoviridae Infections - immunology

Orthomyxoviridae Infections - virology

Receptors, CXCR3 - metabolism

Signal Transduction - drug effects

Details

Title: Subtitle: Chronic Ethanol Consumption Reduces Existing CD8 T Cell Memory and Is Associated with Lesions in Protection against Secondary Influenza A Virus Infections
Creators: Zeb R Zacharias - University of Iowa
Kevin L Legge - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.203(12), pp.3313-3324
DOI: 10.4049/jimmunol.1900770
PMID: 31712384
PMCID: PMC6904436
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: T32 AI007260 / NIAID NIH HHS R21 AA024860 / NIAAA NIH HHS T32 AI007485 / NIAID NIH HHS
Language: English
Date published: 12/15/2019
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984186502902771

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