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Open Access 01-12-2021 | Smoking and Nicotine Detoxification | Research

Long-term cigarette smoke exposure dysregulates pulmonary T cell response and IFN-γ protection to influenza virus in mouse

Authors: Wenxin Wu, Lili Tian, Wei Zhang, J. Leland Booth, Erola Ainsua-Enrich, Susan Kovats, Brent R. Brown, Jordan P. Metcalf

Published in: Respiratory Research | Issue 1/2021

Abstract

Background

Influenza is a highly contagious, acute, febrile respiratory infection caused by a negative-sense, single-stranded RNA virus, which belongs in the Orthomyxoviridae family. Cigarette smoke (CS) exposure worsens influenza infection in terms of frequency and severity in both human and animal models.

Methods

C57BL/6 mice with or without CS exposure for 6 weeks were inoculated intranasally with a single, non-lethal dose of the influenza A virus (IAV) A/Puerto Rico/8/1934 (PR8) strain. At 7 and 10 days after infection, lung and mediastinal lymph nodes (MLN) cells were collected to determine the numbers of total CD4 + and CD8 + T cells, and IAV-specific CD4 + and CD8 + T cells, using flow cytometry. Bronchoalveolar lavage fluid (BALF) was also collected to determine IFN-γ levels and total protein concentration.

Results

Although long-term CS exposure suppressed early pulmonary IAV-antigen specific CD8 + and CD4 + T cell numbers and IFN-γ production in response to IAV infection on day 7 post-infection, CS enhanced numbers of these cells and IFN-γ production on day 10. The changes of total protein concentration in BALF are consistent with the changes in the IFN-γ amounts between day 7 and 10, which suggested that excessive IFN-γ impaired barrier function and caused lung injury at the later stage of infection.

Conclusions

Our results demonstrated that prior CS exposure caused a biphasic T cell and IFN-γ response to subsequent infection with influenza in the lung. Specifically, the number of IAV antigen-specific T cells on day 10 was greatly increased by CS exposure even though CS decreased the number of the same group of cells on day 7. The result suggested that CS affected the kinetics of the T cell response to IAV, which was suppressed at an early stage and exaggerated at a later stage. This study is the first to describe the different effect of long-term CS on T cell responses to IAV at early and late stages of infection in vivo.

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Title: Long-term cigarette smoke exposure dysregulates pulmonary T cell response and IFN-γ protection to influenza virus in mouse
Authors: Wenxin Wu
Lili Tian
Wei Zhang
J. Leland Booth
Erola Ainsua-Enrich
Susan Kovats
Brent R. Brown
Jordan P. Metcalf
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Smoking and Nicotine Detoxification
Influenza
Published in: Respiratory Research / Issue 1/2021
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-021-01713-z

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