Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Pro-Inflammatory Responses in the Intestinal Lymphoid Tissues

It is becoming increasingly apparent that neonates are not immune-compromised, but rather immune-variant. We have described a neonatal model of Yersinia enterocolitica infection in which protective inflammation occurs at the level of the mesenteric lymph nodes (MLN). The expression of pro-inflammatory, but not anti-inflammatory, cytokine genes was markedly induced in the neonatal MLN early after infection. Strikingly, the expression levels in neonates greatly exceeded those seen in infected adults. Elevated pro-inflammatory gene expression was quickly followed by enhanced innate phagocyte recruitment to the MLN of neonates, compared to adults. Neither CD4+ nor B cells were required for inflammation in the neonatal MLN; however, CD4+ and CD8+ cells did increase as well as innate cells as early as 24 hours post-infection. Although MyD88 was shown to be critical in eliciting inflammation in neonates, neither TLR4 nor TLR9 were required. Because Y. enterocolitica contains ligands for multiple TLRs, it is possible that compensation by other TLRs is sufficient to elicit inflammation in the absence of TLR4 or TLR9. Bacterial components were also critical in eliciting high level inflammation in the neonatal MLN. The virulence plasmid of Y. enterocolitica was required for selected pro-inflammatory gene expression and neutrophil recruitment to the neonatal MLN. TNF-alpha protein expression and neutrophil recruitment was markedly enhanced in the neonatal MLN after infection with the delta-yopP strain, while only a modest increase occurred in adults. These models suggest that the level of intestinal inflammation in neonates is critical in determining whether protection or pathology occurs following infection with microbial pathogens