Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses.

successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, interferes with the functions of dendritic cells (DCs), which are the primary antigen-presenting cells of the immune system. We previously showed that dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease Hip1. Here we present data showing that GroEL2, a substrate of Hip1, modulates DC functions. The full-length GroEL2 protein elicited robust proinflammatory responses from DCs and promoted DC maturation and antigen presentation to T cells. In contrast, the cleaved form of GroEL2, which predominates in , was poorly immunostimulatory and was unable to promote DC maturation and antigen presentation. Moreover, DCs exposed to full-length, but not cleaved, GroEL2 induced strong antigen-specific gamma interferon (IFN-γ), interleukin-2 (IL-2), and IL-17A cytokine responses from CD4 T cells. Moreover, the expression of cleaved GroEL2 in the mutant restored the robust T cell responses to wild-type levels, suggesting that proteolytic cleavage of GroEL2 allows to prevent optimal DC-T cell cross talk during infection.