Antigenic role of stress-induced catalase of Salmonella typhimurium in cell-mediated immunity

Abstract

The ability of the H202-induced catalase of Salmonella typhimurium to induce cell-mediated immunity against S. typhimurium infection in mice was examined. When exponentially growing cells of S. typhimurium were treated with 20 ,uM H202, the cells resisted killing by 1 mM H202 and showed the induction of a new species of catalase in addition to the constitutively produced one. Two molecules of catalases in S. typhimurium were isolated from mutant strains: H202-induced catalase (catalase II, 320 kDa), from a regulatory gene-deficient oxyRI mutant, and constitutive catalase (catalase I, 350 kDa), from a katG gene-deleted mutant. When mice were inoculated with a sublethal dose of live cells, an intensive protective immunity (100%b survival at 3 weeks) after challenge with a virulent strain associated with the delayed-type footpad hypersensitivity (DTH) reactions to both catalase I and catalase II was induced. Conversely, mice immunized with formalin-killed virulent S. typhimurium did not elicit protective immunity or DTH to either catalase. When mice were immunized with catalase I or catalase II, an enhanced protection (to a certain extent: 50% survival at 3 weeks) was induced in mice immunized with catalase II associated with DTH which did not cross-react with catalase I but not in those given catalase I. These results suggest that H202-induced stress proteins, including catalase II, are the dominant antigens for cell-mediated immunity in live cells of S. typhimurium and that a burst of such stress proteins in live salmonellae in phagocytes is responsible for the induction of cell-mediated immunity that is largely involved in the protection of susceptible mice against Salmonella infection.

TheSalmonella typhimuriumAhpC Polypeptide Is Not Essential for Virulence in BALB/c Mice but Is Recognized as an Antigen during Infection

“…However, the swelling seen in infected mice was twice that seen in uninfected mice. Moreover, the increase in footpad thickness was maintained at 48 h in infected animals, although the overall thickness ratio declined from that seen at 24 h. In contrast, the effect in uninfected mice was short lived, and the increase in footpad thickness was not found to be significant at 48 h. The swelling induced by AhpC at 24 h in both infected mice (0.52 Ϯ 0.06 mm) and uninfected mice (0.22 Ϯ 0.02 mm) was equivalent to that previously reported for the OxyR-induced enzyme catalase II (37). Notably, injection of the RHFP with mouse albumin did not result in a significant increase in thickness over the thickness of the PBS-injected LHFP (Fig.…”

Oxygen free radicals and systemic autoimmunity

“…ROS are generated by mitochondria through the electron transport chain as toxic by products of oxidative phosphorylation [13]. In addition, free radical production and disturbances in redox status can modulate the expression of a variety of immune and inflammatory molecules [14–16] leading to inflammatory processes, exacerbating inflammation and affecting tissue damage [17]. It has been suggested that abnormal immunity is related to oxidative imbalance [18,19] and antioxidant functions are linked to anti‐inflammatory and/or immunosuppressive properties [20–22].…”

Light emission from a Mudlux transcriptional fusion in Salmonella typhimurium is stimulated by hydrogen peroxide and by interaction with the mouse macrophage cell line J774.2

“…However, several loci which are induced by hydrogen peroxide in vitro in S. typhimurium cells are known to be required for virulence in vivo, including the htrA locus (25) and a locus which encodes an outer membrane protein (36). Furthermore, recent studies have reported that the OxyR-regulated catalase (HP-I) plays a role in eliciting immunological protection against S. typhimurium in mice (27), indicating that expression must occur during the infection process. The transient expression of light by MPG203 suggests that the cell rapidly elicits protective functions in response to hydrogen peroxide and that once the influence of the stimulus has subsided, expression of the gene fusion is again reduced.…”