Comprehensive analyses of pathogen loads and immune responses alongside the gastrointestinal tract upon long-term Salmonella Typhimurium-infection of clinically resistant mice

C57BL/6 mice serve as in vivo-model mimicking acute enteritis caused by Salmonella Typhimurium (S. Tm) but succumb to infection within a week. CBA mice, however, were shown to be clinically resistant to S. Tm-infection, survive the acute phase and are hence suitable to study chronic infection. We performed a comprehensive survey of enteropathogenic loads and immunopathological responses in intestinal compartments during the early and late phase of S. Tm-infection. Upon oral challenge of CBA mice, the enteropathogens colonized the intestines with highest loads in the cecum and colon. Whereas all mice survived the 4-week observation period and did not display any symptoms, marked inflammatory cell damage became overt in the cecum as early as 24 h post-infection (p.i.) that was accompanied by increased numbers of large intestinal innate immune cells including neutrophils, macrophages, and monocytes on days 1 and 14 p.i., whereas recruitment of adaptive immune cells such as T and B lymphocytes and regulatory T cells to the cecum and colon was pronounced on days 14 and 28 p.i. Depending on the time point S. Tm-infection resulted in differential cytokine secretion alongside the intestinal tract. Collectively, our results underscore CBA mice as a model to study chronic S. Tm-infection including long-term fecal pathogen shedding.