Figure 2.

Schematic overview of the presumed infection progression after coinfection of different mouse models with Ye wt and mutant strains. (A) Scheme of the small intestine of SPF-colonized C57BL/6J wild-type mice during homeostasis (left), after initial disturbance (mid), and expected outcome after co-infection with a 1:1 mixture of Ye wt and an attenuated mutant strain. Initially, the gut lumen in SPF mice is densely colonized with a complex microbiota. Ye infection, associated with an infiltration of microfold cells (M-cells) mainly conducted by the wt strain, leads to an unspecific antimicrobial immune response accompanied by the release of phagocytic cells into the gut lumen and augmented expression of antimicrobial proteins (AMPs, Reg3γ, defensins) by epithelial cells. Both the antimicrobial response and inflammation affect at least parts of the microbiota and reduce its complexity and density. Whereas Ye wt can counteract phagocytosis by injection of effectors into immune cells, thereby killing them, the Ye mutant strain is more susceptible to phagocytosis and killing by immune cells and, thus, is finally outcompeted 14 days after infection onset. (B) Schematic overview of expected Ye wt and mutant CFU in feces during the infection course (upper diagram) and the presumed strength of host immune response and colonization resistance (CR; bottom diagram). (C) In germ-free (GF) mice that lack a microbiota that confers CR and harbor an immature immune system, Ye wt and mutant strains are both able to colonize the gut lumen and do not necessarily need to enter a site near the mucosa to colonize the gut effectively. This leads to weak antimicrobial responses that Ye can cope with, without the necessity to possess specific virulence traits (such as YadA or a functional T3SS). This results in comparable numbers of wt and mutant strains at the end of the observation period. (D) Presumed CFUs of Ye wt and mutant strain in feces of GF mice (upper diagram). The immune responses in GF animals are less potent as compared to C57BL/6J wild-type mice, while microbial CR is absent (bottom diagram). (E) In SPF-colonized MyD88^−/− mice, we assume that the strongly limited immune reaction does not significantly affect the CR that is mediated by the endogenous microbiota. This will, presumably, result in a lower overall Ye cell count in the gut compared to the SPF wild-type and GF mice. The immune deficiency entails an almost contingent infection outcome (right panel), resulting in either comparable numbers of the Ye wt and the mutant strains, or one of the strains becoming more abundant at two days after infection. Please note that the infection course in the MyD88^−/− mice can only be monitored for a shorter period due to adherence to animal welfare regulations. (F) The presumed coincidental CFU development in feces is illustrated by overlapping, shaded areas (upper diagram). Limited immune responses reduce CR to a low level (bottom diagram); dpi = days post-infection.