Citrobacter rodentium is a mouse pathogen that mimics many virulence behaviours of the human pathogen enteropathogenic E. coli and is commonly used as a model organism in the investigation of the enteric mucosal immune response. C. rodentium is commonly described in the literature as inducing a Th1-, Th17-, ILC3-mediated immune response where IL-22 is critical for maintaining epithelial integrity and promoting the production of anti-microbial peptides. However, a recent paper by Aychek, et al, (2015) indicates that Th1 cells may, in fact, be detrimental in the host response to C. rodentium infection.
This study aims to clarify the role of Th1 cells in the intestinal immune response. The differentiation naïve T cells into pro-inflammatory Th1 is dependent on the heterodimeric cytokine IL-12 which is expressed by dendritic cells and macrophages. IL-12 is made up of two subunits, IL-12p35 which is unique to IL-12, and IL-12p40 which can also be part of IL-23. To date, all studies into IL-12 in the C. rodentium immune response have utilised IL-12p40-/- mice, which are also be deficient in IL-23 and therefore Th17 cells. Our study shows that IL-12p35-/- mice, deficient in IL-12 and Th1 cells, are able to contain and clear C. rodentium infection as well as C57BL/6 mice. Histologically, there was increased inflammation observed in the laminar propria of infected IL-12p35-/- mice compared C57BL/6 mice and increased penetration of the bacteria into the crypts. Overall, however, these data suggest that IL-12 and Th1 cells are largely dispensable in the host response to C. rodentium infection.