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-γ and IFN-γ-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-γ-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-γ-activated Prdx1-/-than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, Nω-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-γ-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.
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Kazunori
K
Matsumura
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Hiroki
0000-0001-8807-3957
H
Iwai
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Masako
M
Kato-Miyazawa
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Fumiko
F
Kirikae
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Jizi
J
Zhao
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; and.
Toru
T
Yanagawa
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; and.
Tetsuro
T
Ishii
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
Tohru
T
Miyoshi-Akiyama
Department of Microbiology, Tochigi Prefectural Institute of Public Health and Environmental Science, Utsunomiya, Tochigi 329-1196, Japan.
Keiji
K
Funatogawa
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan; tkirikae@ri.ncgm.go.jp.
Teruo
T
Kirikae
D000818:Animals; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D054464:Peroxiredoxins / Q000172:deficiency / Q000276:immunology*
D018664:Interleukin-12; D009569:Nitric Oxide; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse