Protective Role of Peroxiredoxin I in Heat-KilledStaphylococcus Aureus-infected Mice

Abstract

Background/Aim: Staphylococcus aureus (S. aureus) is a major gram-positive pathogen, which can cause toxic and immunogenic injuries both in nosocomial and community-acquired infections. Peroxiredoxin (Prx) I plays crucial roles in cellular apoptosis, proliferation, and signal transduction as well as in immunoregulation. The present study aimed to investigate whether Prx I protects mice from death caused by the heat-killed Staphylococcus aureus. Materials and Methods: In the present study, we challenged the wild-type and Prx I-deficient mice with heat-killed S. aureus (HKSA). The effects of Prx I were evaluated by a series of in vitro and in vivo experiments including western blot, Haematoxylin and Eosin staining, splenocyte analysis and cytokines analysis. Results: Intra-peritoneal (ip) inoculation of HKSA resulted in increased mortality of Prx I-knockout (KO) mice with severe liver damage and highly populated spleens with lymphocytes. Furthermore, HKSA infections also bursted the production of both pro-inflammatory and antiinflammatory serum cytokines in Prx I KO compared to wildtype mice. Conclusion: Enhanced mortality of S. aureusinfected mice with Prx I deficiency suggested that Prx I may protect against the infection-associated lethality of mice. Peroxiredoxin (Prx) I, an antioxidant enzyme, belongs to 2-cysteine Prxs (1). Recent evidence shows that Prx I participates in several cellular signaling pathways by interacting with diver proteins to regulate cell differentiation, apoptosis and proliferation (2-4). Accumulation of reactive oxygen species (ROS) in cells can cause oxidation of DNA, membrane lipids and proteins, resulting in increased cellular damage (5). Prx I plays an important role in scavenging ROS in cells (6). In the last decade, the regulatory role of Prx I in tumorigenesis has been well defined both in vivo and in vitro. Depletion of Prx I can spontaneously induce the development of several malignant cancers and severe haemolytic anaemia, as well as oxidative DNA damage and decreased cell proliferation (7). Furthermore, a previous study by our group has also shown that Prx I suppresses the K-ras-induced lung carcinogenesis via the ROS/ERK/cyclin D1 signaling pathway (8), suggesting that Prx I may be a tumor suppressor that could prevent carcinogenesis.

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].…”

Release of redox enzymes and micro-RNAs in extracellular vesicles, during infection and inflammation

“…There are several studies on the potential anti-inflammatory action of TXN and PRDX associated with their "antioxidant" action (for instance: [114][115][116]). Although these studies deal with redox regulation by intracellular enzymes, that are not the subject of this review, extracellular TXN or PRDX can potentially be taken up by other cells to increase their intracellular levels (Figure 4).…”

Heat-Killed Staphylococcus aureus Induces Bone Mass Loss through Telomere Erosion

“…S. aureus is a common cause of chronic inflammation and is known to contribute to the development of various chronic inflammatory conditions such as osteomyelitis, chronic liver abscess, and septic arthritis [ 13 , 14 , 15 ]. In this study, we constructed a systemic chronic inflammation model using heat-killed S. aureus (HKSA), as HKSA is a well-established model of chronic inflammation, such as lung injury, enterocyte effacement, intestinal epithelium destruction, allowing us to mimic persistent inflammation without the risk of additional infections [ 16 , 17 , 18 , 19 ].…”