Pulmonary immunization with a recombinant influenza A virus vaccine induces lung-resident CD4+memory T cells that are associated with protection against tuberculosis

Autor: Flórido, Manuela, Muflihah, Heni, Lin, Leon C.W., Xia, Yingju, Sierro, Frederic, Palendira, Mainthan, Feng, Carl G., Bertolino, Patrick, Stambas, John, Triccas, James A., Britton, Warwick. J.
Zdroj: Mucosal immunology; November 2018, Vol. 11 Issue: 6 p1743-1752, 10p
Abstrakt: The lung is the primary site of infection with the major human pathogen, Mycobacterium tuberculosis. Effective vaccines against M. tuberculosismust stimulate memory T cells to provide early protection in the lung. Recently, tissue-resident memory T cells (TRM) were found to be phenotypically and transcriptional distinct from circulating memory T cells. Here, we identified M. tuberculosis-specific CD4+T cells induced by recombinant influenza A viruses (rIAV) vaccines expressing M. tuberculosispeptides that persisted in the lung parenchyma with the phenotypic and transcriptional characteristics of TRMs. To determine if these rIAV-induced CD4+TRMwere protective independent of circulating memory T cells, mice previously immunized with the rIAV vaccine were treated with the sphingosine-1-phosphate receptor modulator, FTY720, prior to and during the first 17 days of M. tuberculosischallenge. This markedly reduced circulating T cells, but had no effect on the frequency of M. tuberculosis-specific CD4+TRMsin the lung parenchyma or their cytokine response to infection. Importantly, mice immunized with the rIAV vaccine were protected against M. tuberculosisinfection even when circulating T cells were profoundly depleted by the treatment. Therefore, pulmonary immunization with the rIAV vaccine stimulates lung-resident CD4+memory T cells that are associated with early protection against tuberculosis infection.
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