HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria

  • Kalsdorf B
  • Scriba T
  • Wood K
 et al. 
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Abstract

RATIONALE: The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease. OBJECTIVES: To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis. METHODS: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot. MEASUREMENTS AND MAIN RESULTS: Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001). Mycobacteria (bacillus Calmette-Guerin)-specific CD4 T-cell responses in BAL were severely impaired: Frequencies of cells expressing IFN-gamma or tumor necrosis factor (TNF)-alpha, as well as polyfunctional cells, expressing IFN-gamma, TNF-alpha, and IL-2 together, were lower in HIV-1-infected persons than in uninfected controls (P < 0.01 for all). CONCLUSIONS: In addition to a total CD4 T-cell deficit, the function of mycobacteria-specific CD4 T cells is significantly impaired in the lung of HIV-1-infected persons, which may account for the HIV-1-associated elevated risk for developing tuberculosis.

Author-supplied keywords

  • HIV-1
  • Immunity mucosal
  • Macrophages
  • T-cells
  • Tuberculosis

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Authors

  • Barbara Kalsdorf

  • Thomas J. Scriba

  • Kathryn Wood

  • Cheryl L. Day

  • Keertan Dheda

  • Rodney Dawson

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