AttenuatedYersiniaenterocoliticaMutant Strains Exhibit Differential Virulence in Cytokine-Deficient Mice: Implications for the Development of Novel Live Carrier Vaccines

Abstract

Yersinia enterocolitica mutant strains, including mutants deficient in the chaperone

Lack of TNFR p55 Results in Heightened Expression of IFN-γ and IL-17 during the Development of Reactive Arthritis

“…However, TNF is also a critical cytokine in the protective host response against bacterial infection, including Y. enterocolitica (5,24), raising the question as to whether this cytokine plays a pathogenic or protective role in bacterial-induced ReA, a pathological entity that combines components of infection and autoimmunity. We recently demonstrated that TNFR p55 signaling confers protection against ReA induced by Y. enterocolitica O:3 (8).…”

“…This cytokine was shown to be fundamental in turning acute synovitis into a chronic destructive arthritis (28,29). In contrast, IFN-g is strongly induced by Yersinia infection (18,24) and is essential for initiating joint inflammation in several arthritis models (30 (Fig. 3A).…”

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

“…We previously demonstrated that Y. enterocolitica ⌬sycH, a functional YopH mutant, colonizes the PP without causing systemic infection, indicating that yersiniae lacking the YopH function can be eliminated by mechanisms that do not require an interleukin-12 (IL-12), IL-18-, and tumor necrosis factor receptor p55 (TNF-Rp55)-dependent immune defense (7). Further studies demonstrated that gamma interferon (IFN-␥) and IL-6 are not necessarily required for clearance of Y. enterocolitica ⌬yopH (38).…”

“…All animal procedures were performed according to the rules and standards for the use of laboratory animals of the U.S. (23). Bacteria were cultured and prepared as previously described (7). For infection, mice were first starved for 3 h before and after orogastric infection with 5 ϫ 10 8 yersiniae in 0.2 ml phosphate-buffered saline (PBS) using a gastric tube.…”

“…In coinfection experiments, the Y. enterocolitica WT clearance was calculated as the differential CFU number between plates with and without kanamycin, since Y. enterocolitica ⌬yopH is kanamycin resistant. The limit of CFU detection is log 10 of 25 CFU ϭ 1.4 (7).…”