The innate immune response is critical to enteric disease resistance and the induction of mucosal adaptive immunity. In mucosae of the small intestine, Peyer's patches play a central role in immune surveillance and sampling of bacteria by specialized M cells. The innate immune response to Salmonella enterica serovar Choleraesuis, an enteric pathogen of swine, involves IL-1β and IL-8 mRNA induction but not that of IL-6 and TNFα, in contrast to Salmonella serovar Typhimurium infection of murine small intestine. We investigated in vivo responses to Salmonella and potential effects of animal variation since the gut environment is highly dynamic and constantly changing physiologically. Salmonella serovar Choleraesuis induced an early proinflammatory cytokine response at 6 h after infection, which was characterized by a 4-fold increase in production of CXCL2 mRNA by jejunal Peyer's patches (JPP), and a 12-fold increase in IL-1β and 4-fold increase in IL-8 (CXCL8) mRNAs by distal ileal Peyer's patches (IPP). Levels of IL-1β and IL-8 mRNA were positively correlated with numbers of mucosal neutrophils in the distal IPP. Salmonella DNA was also detected in ileal tissues, including Peyer's patches, absorptive epithelium and mesenteric lymph nodes, in 33-83% of infected animals, compared to the jejunal tissues, which were positive in 0-33% of infected pigs. Notwithstanding substantial animal-to-animal variation, IL-1β was increased in both proximal and distal IPP, IL-8 was increased in the distal IPP, and calprotectin was associated with both by cluster analysis. These data indicate that IL-1β and IL-8 expression in the IPP plays a key role early in the interaction between Salmonella serovar Choleraesuis and the small intestine.
Bibliographical noteFunding Information:
This investigation was supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service, Grant Number 2002-35204-11705 and NIH Grants R01 DA-10200 and T32 DA-07097. KAH was supported by the NIH/NIDA training Grant T32-DA-07239. The authors thank Dr. Roy Curtiss III (Department of Biology, Washington University, St. Louis, MO), who generously provided Salmonella enterica serovar Choleraesuis strain χ3246, and Dr. David Brown, Department of Veterinary and Biomedical Sciences, University of Minnesota, for thoughtful discussions and suggestions. The authors also wish to thank Drs. Zheng Jin Tu and Wayne Xu at the University of Minnesota Supercomputing Institute for bioinformatics support. Colleen Finnegan assisted with the qRT-PCR, and Amanda Helvig performed the immunohistochemistry analysis (including Fig. 1 ).
- Peyer's patch
- Veterinary immunology