Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Peroxiredoxin (PRDX)1 is an antioxidant that detoxifies hydrogen peroxide and peroxinitrite. Compared with wild-type (WT) mice, Prdx1-deficient (Prdx1(-/-)) mice showed increased susceptibility to Mycobacterium tuberculosis and lower levels of IFN-gamma and IFN-gamma- producing CD4(+) T cells in the lungs after M. tuberculosis infection. IL-12 production, c-Rel induction, and p38 MAPK activation levels were lower in Prdx1(-/-) than in WT bone marrow-derived macrophages (BMDMs). IFN-gamma-activated Prdx1(-/-) BMDMs did not kill M. tubercuosis effectively. NO production levels were lower, and arginase activity and arginase 1 (Arg1) expression levels were higher, in IFN-gamma-activated Prdx1(-/-) than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, N-omega-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-gamma-activated Prdx1(-/-) BMDMs after M. tuberculosis infection. These results suggest that PRDX1 contributes to host defenses against M. tuberculosis. PRDX1 positively regulates IL-12 production by inducing c-Rel and activating p38 MAPK, and it positively regulates NO production by suppressing Arg1 expression in macrophages infected with M. tuberculosis.