The increased protection and pathology in Mycobacterium tuberculosis-infected IL-27R-alpha-deficient mice is supported by IL-17A and is associated with the IL-17A-induced expansion of multifunctional T cells.

摘要: During Mycobacterium tuberculosis (Mtb) infection, mice lacking the IL-27R exhibit lower bacterial burdens but develop an immunopathological sequelae in comparison to wild-type mice. We here show that this phenotype correlates with enhanced recruitment of antigen-specific CCR6+ CD4+ T cells and increased frequency IL-17A-producing cells. By comparing outcome Mtb infection C57BL/6, IL-27R-deficient IL-27R/IL-17A-double deficient mice, we observed both protection elevated immunopathology are supported by IL-17A. Whereas IL-17A neither impacts development Tr1 nor expression PD1 KLRG1 on during it regulates presence multifunctional T-cells lungs, co-expressing IFN-γ, IL-2 TNF. Eventually, supports Cxcl9, Cxcl10 Cxcl13 granulomatous response lungs infected Taken together, contributes Mtb-infected probably through a chemokine-mediated strategic positioning granulomas. As IL-27 limits optimal antimycobacterial inhibiting production, blocking IL-27R-mediated signaling may represent strategy for improving vaccination host-directed therapy tuberculosis. However, because also prevents IL-17A-mediated immunopathology, such intervention has be tightly controlled.