Previously, it was shown that optimal functioning of the Yersinia type III secretion system (T3SS) in cell culture infection assays requires the exoribonuclease polynucleotide phosphorylase (PNPase) and that normal T3SS activity could be restored in the Deltapnp strains by expressing just the approximately 70-aa S1 RNA-binding domain of PNPase. Here, it is shown that the Yersinia Deltapnp strain is less virulent in the mouse compared with the isogenic wild-type strain. To begin to understand what could be limiting T3SS activity in the absence of PNPase, T3SS-encoding transcripts and proteins in the YersiniaDeltapnp strains were analyzed. Surprisingly, it was found that the Deltapnp Yersinia strains possessed enhanced levels of T3SS-encoding transcripts and proteins compared with the wild-type strains. We then found that an S1 variant containing a disruption in its RNA-binding subdomain was inactive in terms of restoring normal T3SS activity. However, T3SS expression levels did not differ between Deltapnp strains expressing active and inactive S1 proteins, further showing that T3SS activity and expression levels, at least as related to PNPase and its S1 domain, are not linked. The results suggest that PNPase affects the expression and activity of the T3SS by distinct mechanisms and that the S1-dependent effect on T3SS activity involves an RNA intermediate.

TRIF signaling triggers the amplification of macrophage bactericidal activity sufficient to eliminate invading intestinal pathogens through the sequential induction of IFN-β and IFN-γ from macrophages and NK cells, respectively.

Neonates are considered highly susceptible to gastrointestinal infections. This susceptibility has been attributed partially to immaturity in immune cell function. To study this phenomenon, we have developed a model system with murine neonates, using the natural orogastric route of transmission for the enteropathogen Yersinia enterocolitica. The susceptibilities of 7-day-old and adult mice to orogastric Y. enterocolitica infection were assessed in 50% lethal dose experiments. Remarkably, neonatal mice of either the BALB/c or C57BL/6 mouse strain showed markedly enhanced survival after infection compared to adult mice. The resistance of neonates was not due to failure of the bacteria to colonize neonatal tissues; Y. enterocolitica was readily detectable in the intestine and mesenteric lymph nodes (MLN) for at least 1 week after infection. In adult mice, Y. enterocolitica rapidly disseminated to the spleen and liver. In striking contrast, bacterial invasion of the spleen and liver in neonates was limited. Using flow cytometry and histology, we found substantial increases in the percentages of neutrophils and macrophages in the neonatal MLN, while influx of these cells into the adult MLN was limited. Similar results were obtained using two different high-virulence Y. enterocolitica strains. Importantly, depletion of neutrophils with a specific antibody led to increased translocation of the bacteria to the spleens and livers of neonates. Together, these experiments support the hypothesis that the neonatal intestinal immune system can rapidly mobilize innate phagocytes and thereby confine the bacterial infection to the gut, resulting in a high level of resistance.

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