Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Abstract

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.

Targeting Peroxiredoxin 1 by a Curcumin Analogue, AI-44, Inhibits NLRP3 Inflammasome Activation and Attenuates Lipopolysaccharide-Induced Sepsis in Mice

“…In esophageal squamous cell carcinoma, PRDX1 functioned as a tumor suppressor (22), whereas in oral squamous cell carcinoma, PRDX1 was overexpressed and might be a biomarker for the diagnosis and prognosis (23). Additionally, PRDX1 is proven to be essential for antitumor activity of NK cells and antiviral activity of macrophages (24,25). However, the role of PRDX1 in the NLRP3 inflammasome remains unclear.…”

Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis

“…CR also led to a significant increase of serpinb3a, described as critical for epidermal barrier homeostasis and with a role in the initiation of the acute inflammatory response (Sivaprasad et al, 2011(Sivaprasad et al, , 2015, and serpinb12, an abundant intracellular serpin expressed in most surface and epithelial tissues, such as lung, with a biologic function in cellular barrier and defense from environmental stimuli (Figure 7B) (Niehaus et al, 2015). Finally, proteins involved in protection from tissue damage and cell stress such as aldehyde dehydrogenase and peroxiredoxin were also upregulated in CR MTB animals (Matsumura et al, 2016;Park et al, 2014).…”

Knockout Mouse Models for Peroxiredoxins

“…Prdx1 deficiency attenuates cisplatin-induced nephrotoxicity [37]. Studies using Prdx1-knockout mouse models also show that PRDX1 is involved in maintenance of stemness of mouse embryonic stem cells by suppression of ROS/JNK-induced neurogenesis [38], modulation of cellular senescence in mouse embryonic fibroblasts (MEFs) [39], host defenses against Mycobacterium tuberculosis and Staphylococcus aureus [40,41], and maintenance of progesterone production in the corpus luteum through regulating the unfolded protein response [42].…”