Robust innate immune responses of murine neonates following orogastric Yersinia enterocolitica exposure (44.13)

Abstract

Abstract Neonates are generally thought to be highly susceptible to gastrointestinal disease, owing in part to immaturity in immune function. To study this phenomenon experimentally, we have developed a murine pediatric model of infection with the Gram-negative bacterium Yersinia enterocolitica (Ye). This model is highly relevant to the human pediatric population since Ye is a prevalent cause of gastrointestinal disorders in young children. LD50 experiments were performed on 7 day old and adult mice infected orogastrically with Ye. Remarkably, BALB/c or C57BL/6 neonatal mice were up to 50 times more resistant than adult mice. Bacterial colonization experiments indicated that Ye rapidly disseminated to the spleen and liver in adults. In striking contrast, colonization of the neonatal spleen and liver was very limited. Instead, bacterial colonization in neonates was largely restricted to the intestine and mesenteric lymph nodes (MLN). Flow cytometric and histological studies revealed markedly increased levels of neutrophils and macrophages in the neonatal MLN after infection. Importantly, in vivo neutrophil depletion led to efficient dissemination of the bacteria to the spleen and liver of neonates. Therefore, in response to some enteric bacteria, neonates appear to be able to mount vigorous mucosal immune responses, rapidly mobilizing innate phagocytes, and confining the bacterial infection to the gut. This work was supported by NIAID grant R01 AI44923-02 (B.A.), NIAID Public Health Service grant AI53459 (K.S.), and the Department of Microbiology and Immunology, University of Miami.