Campylobacter jejuni infections have a high prevalence worldwide and represent a 
significant socioeconomic burden. C. jejuni can cross the intestinal epithelial 
barrier as visualized in biopsies derived from human patients and animal models, 
however, the underlying molecular mechanisms and associated immunopathology are 
still not well understood. We have recently shown that the secreted serine 
protease HtrA (high temperature requirement A) plays a key role in C. jejuni 
cellular invasion and transmigration across polarized epithelial cells in vitro. 
In the present in vivo study we investigated the role of HtrA during C. jejuni 
infection of mice. We used the gnotobiotic IL-10(-/-) mouse model to study 
campylobacteriosis following peroral infection with the C. jejuni wild-type (WT) 
strain NCTC11168 and the isogenic, non-polar NCTC11168ΔhtrA deletion mutant. Six 
days post infection (p.i.) with either strain mice harbored comparable 
intestinal C. jejuni loads, whereas ulcerative enterocolitis was less pronounced 
in mice infected with the ΔhtrA mutant strain. Moreover, ΔhtrA mutant infected 
mice displayed lower apoptotic cell numbers in the large intestinal mucosa, less 
colonic accumulation of neutrophils, macrophages and monocytes, lower large 
intestinal nitric oxide, IFN-γ, and IL-6 as well as lower TNF-α and IL-6 serum 
concentrations as compared to WT strain infected mice at day 6 p.i. Notably, 
immunopathological responses were not restricted to the intestinal tract given 
that liver and kidneys exhibited mild histopathological changes 6 days p.i. with 
either C. jejuni strain. We also found that hepatic and renal nitric oxide 
levels or renal TNF-α concentrations were lower in the ΔhtrA mutant as compared 
to WT strain infected mice. In conclusion, we show here that the C. jejuni HtrA 
protein plays a pivotal role in inducing host cell apoptosis and immunopathology 
during murine campylobacteriosis in the gut in vivo.