Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection

Manuela Flórido, Michael A. Grima, Caitlin M. Gillis, Yingju Xia, Stephen J. Turner, James A. Triccas, John Stambas, Warwick J. Britto

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Guérin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA257-264 failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c+ dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.

Original languageEnglish
Pages (from-to)302-311
Number of pages10
JournalJournal of Immunology
Volume191
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013
Externally publishedYes

Cite this

Flórido, Manuela ; Grima, Michael A. ; Gillis, Caitlin M. ; Xia, Yingju ; Turner, Stephen J. ; Triccas, James A. ; Stambas, John ; Britto, Warwick J. / Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection. In: Journal of Immunology. 2013 ; Vol. 191, No. 1. pp. 302-311.
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title = "Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection",
abstract = "Individuals infected with mycobacteria are likely to experience episodes of concurrent infections with unrelated respiratory pathogens, including the seasonal or pandemic circulating influenza A virus strains. We analyzed the impact of influenza A virus and mycobacterial respiratory coinfection on the development of CD8 T cell responses to each pathogen. Coinfected mice exhibited reduced frequency and numbers of CD8 T cells specific to Mycobacterium bovis bacille Calmette-Gu{\'e}rin (BCG) in the lungs, and the IFN-γ CD8 T cell response to BCG-encoded OVA was decreased in the lungs of coinfected mice, when compared with mice infected with BCG alone. Moreover, after 2 wk of infection, mice coinfected with both pathogens showed a significant increase in the number of mycobacteria present in the lung compared with mice infected with BCG only. Following adoptive transfer into coinfected mice, transgenic CD8 T cells specific for OVA257-264 failed to proliferate as extensively in the mediastinal lymph nodes as in mice infected only with BCG-OVA. Also noted was a reduction in the proliferation of BCG-specific CD4 transgenic T cells in mice coinfected with influenza compared with mice infected with BCG alone. Furthermore, phenotypic analysis of CD11c+ dendritic cells from mediastinal lymph nodes of the infected mice showed that coinfection was associated with decreased surface expression of MHC class II and class I. Thus, concurrent pulmonary infection with influenza A virus is associated with decreased MHC expression on dendritic cells, reduced activation of BCG-specific CD4 and CD8 T cells, and impaired clearance of mycobacteria.",
author = "Manuela Fl{\'o}rido and Grima, {Michael A.} and Gillis, {Caitlin M.} and Yingju Xia and Turner, {Stephen J.} and Triccas, {James A.} and John Stambas and Britto, {Warwick J.}",
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Influenza A virus infection impairs mycobacteria-specific T cell responses and mycobacterial clearance in the lung during pulmonary coinfection. / Flórido, Manuela; Grima, Michael A.; Gillis, Caitlin M.; Xia, Yingju; Turner, Stephen J.; Triccas, James A.; Stambas, John; Britto, Warwick J.

In: Journal of Immunology, Vol. 191, No. 1, 01.07.2013, p. 302-311.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Flórido, Manuela

AU - Grima, Michael A.

AU - Gillis, Caitlin M.

AU - Xia, Yingju

AU - Turner, Stephen J.

AU - Triccas, James A.

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AU - Britto, Warwick J.

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