Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses.

Abstract

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 thatdampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease Hip1. Here we present data showing thatGroEL2, 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 CD4T cells. Moreover, the expression of cleaved GroEL2 in themutant restored the robust T cell responses to wild-type levels, suggesting that proteolytic cleavage of GroEL2 allowsto prevent optimal DC-T cell cross talk duringinfection.