Understanding how Mycobacterium tuberculosis alters the T helper response via the type 7 secretion system ESX-1 and lipid virulence factor phthiocerol dimycocerosate 9183

Description Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, causes more deaths worldwide annually than any other pathogen. Mtb growth in the lungs becomes controlled once the adaptive immune response is activated. CD4+ T helper cells have been shown to be undoubtedly important for controlling Mtb. Which CD4+ T helper subset(s) and cytokines important for controlling Mtb infection is not completely understood. Recent reports of human and non-human primate data indicates that type 17 T helper (Th17) cells provide a protective role against Mtb infection, although the role of Th17s in the murine model of tuberculosis remains unclear with conflicting reports of protection. Additional understanding of which and how T helper responses promote host control of Mtb infection is necessary for development of an efficacious vaccine against Mtb. We discovered mice lacking the ability to induce Th1s had instead responded to Mtb infection with a Th17 response with protection mediated by IL-17a. The Esat-6 secretion system (ESX-1) and lipid virulence factor phthiocerol dimycocerosate (PDIM) of Mtb are the causes for the lack of Th17 induction in mice during infection. The type I interferon response induced by ESX-1 and PDIM only boost the type 1 T helper (Th1) response and is not the reason why Th17s are not induced during wild-type Mtb infection. Finally, we show that mice lacking a Th17 response can be treated with exogenous IL-17a for modest protection against Mtb infection. Funding Sources Supported by NIH AI063302 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)