Over millennia of infecting humans, Mycobacterium tuberculosis has evolved numerous ways to manipulate host immune responses. In Mucosal Immunology, Xing and colleagues identify a mechanism through which M. tuberculosis dampens the induction of TH1 cells, a response critical for controlling infection by this bacterium. Mouse hosts deficient in the adaptor DAP12 have more robust TH1 responses and a lower bacterial burden in both the spleen and lungs following infection with M. tuberculosis. Mechanistically, DAP12 is required for induction of the negative regulatory kinase IRAK-M following the infection of antigen-presenting cells (APCs) with M. tuberculosis. Activated IRAK-M triggers production of the immunosuppressive cytokine IL-10, and such APCs are ineffective at priming TH1 responses in lung-draining lymph nodes. By upregulating IRAK-M via DAP12 in host APCs, M. tuberculosis has yet another means by which it can thwart effective immune responses.

Mucosal Immunol. 7, 670–683 (2014)