IL-32 and its splice variants are associated with protection against Mycobacterium tuberculosis infectionand skewing of Th1/Th17 cytokines

[摘要] Studies in IL-32 transgenic mice and in vitro suggest that IL-32 may have protective effects against Mycobacterium tuberculosis, but so far there are barely any studies in humans. We studied the role of IL-32 and its splice variants in tuberculosis (TB) in vivo and in vitro. Blood transcriptional analysis showed lower total IL-32 mRNA levels in pulmonary TB patients compared to patients with latent TB infection and healthy controls. Also, among Indonesian household contacts who were heavily exposed to an infectious TB patient, IL-32 mRNA levels were higher among those who remained uninfected compared to those who became infected with M. tuberculosis. In peripheral blood mononuclear cells from healthy donors, we found that IL-32?, the most potent isoform, was down-regulated upon M. tuberculosis stimulation. This decrease in IL-32? was mirrored by an increase of another splice variant, IL-32?. Also, a higher IL-32?/IL-32? ratio correlated with IFN-? production, whereas a lower ratio correlated with production of IL-1Ra, IL-6, and IL-17. These data suggest that IL-32 contributes to protection against M. tuberculosis infection, and that this effect may depend on the relative abundance of different IL-32 isoforms.

[学科分类] 生理学

[关键词] tuberculosis;Mycobacterium tuberculosis;immune response;interleukin-32;cytokines