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-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 OVA(257-264) 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.
authors.affiliation: Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia. m.florido@centenary.org.au
authors.forename: Manuela
authors.initials: M
authors.lastname: Flórido
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grima
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Gillis
authors.forename: Yingju
authors.initials: Y
authors.lastname: Xia
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology* / Q000821:virology
chemical_list: D010047:Ovalbumin