Murine Neonates Are Highly Resistant toYersinia enterocoliticafollowing Orogastric Exposure

Abstract

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.

Role of YopK in Yersinia pseudotuberculosis Resistance against Polymorphonuclear Leukocyte Defense

“…For this purpose, we analyzed the presence of PMNs, which are recruited to PPs upon infection as a result of the inflammatory response (38)(39)(40). Sections of PPs from mice infected with the yopK mutant or the wild-type strain were subjected to immunohistochemistry staining of PMNs.…”

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

“…In contrast to the vast majority of experimental systems, we recently demonstrated (20) that murine neonates are highly resistant to oral infection with the Gram-negative enteropathogen Yersinia enterocolitica. The resistance of neonatal mice infected with Y. enterocolitica was associated with robust innate inflammation, characterized by the recruitment of high levels of neutrophils and macrophages into the intestinal tissue (20).…”

Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

“…We recently discovered that murine neonates are highly resistant to orogastric infection with the Gram-negative enteropathogen Y. enterocolitica (22). Here, we report that this resistance is associated with the rapid and vigorous mobilization of the intestinal innate immune system.…”

“…However, relatively little is known about intestinal inflammation in a setting of protection against infection in neonates. Recently, we have discovered that 7-day-old neonatal mice are as resistant to the Gram-negative enteropathogen Yersinia enterocolitica as adults (22,23). Notably, infected neonates mobilize high frequencies of innate phagocytes which are essential for protection against peripheral dissemination of the bacteria.…”

“…CD4 Ϫ/Ϫ mice were generously provided by R. Levy Animal infections. Bacterial frozen stocks (22) were washed twice with Hank's balanced salt solution (HBSS; Gibco, Grand Island, NY) and diluted to the desired concentration with 0.1% blue food coloring (McCormick, Baltimore, MD). Neonates and adults were inoculated with 5 ϫ 10 8 CFU, unless otherwise indicated.…”