Natural killer cells are recruited during pulmonary tuberculosis and their ex vivo responses to mycobacteria vary between healthy human donors in association with …

D Portevin, LE Via, S Eum, D Young - Cellular microbiology, 2012 - Wiley Online Library
D Portevin, LE Via, S Eum, D Young
Cellular microbiology, 2012Wiley Online Library
Humans vary widely in their susceptibility to tuberculosis. While only a minority will progress
to disease, the majority of healthy individuals exposed to M ycobacterium tuberculosis
mount an immune response that can clear or contain the infection in a quiescent form. Using
immunofluorescence on human clinical samples, we identified natural killer (NK) cells
infiltrating granulomatous pulmonary lesions during active disease. In order to compare the
NK cell ability to react to free mycobacteria in the context of tuberculosis infection and M …
Summary
Humans vary widely in their susceptibility to tuberculosis. While only a minority will progress to disease, the majority of healthy individuals exposed to Mycobacterium tuberculosis mount an immune response that can clear or contain the infection in a quiescent form. Using immunofluorescence on human clinical samples, we identified natural killer (NK) cells infiltrating granulomatous pulmonary lesions during active disease. In order to compare the NK cell ability to react to free mycobacteria in the context of tuberculosis infection and Mycobacterium bovis BCG vaccination, NK cells were isolated from the peripheral blood of anonymous healthy human donors, and stimulated with M. tuberculosis H37Rv or M. bovis BCG. Extracellular M. tuberculosis and M. bovis BCG could equally trigger the release of IFNγ and TNFα from NK cells in the presence of IL‐2. However, we found that this response varied 1000‐fold between individuals (n = 52), with differences in KIR haplotype providing a significant criterion to distinguish between low and high responders. Our findings suggest that variations at the KIR locus and therefore of the NK cell repertoire may affect cytokine production in response to mycobacteria and we propose that this innate variability couldsustain different levels of susceptibility to M. tuberculosis infection.
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