Interleukin-1 (IL-1) signaling in intestinal stromal cells controls KC/ CXCL1 secretion, which correlates with recruitment of IL-22- secreting neutrophils at early stages of Citrobacter rodentium infection

• Published in: Infection and immunity Vol. 83; no. 8; pp. 3257 - 3267
• Main Authors: Lee, Yong-Soo, Yang, Hyungjun, Yang, Jin-Young, Kim, Yeji, Lee, Su-Hyun, Kim, Ji Heui, Jang, Yong Ju, Vallance, Bruce A, Kweon, Mi-Na
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.08.2015
• Subjects: Animals; Cells, Cultured; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Citrobacter rodentium; Citrobacter rodentium - physiology; Enterobacteriaceae Infections - genetics; Enterobacteriaceae Infections - metabolism; Enterobacteriaceae Infections - microbiology; Escherichia coli; Female; Host Response and Inflammation; Humans; Interleukin-1 - genetics; Interleukin-1 - metabolism; Interleukin-22; Interleukins - genetics; Interleukins - metabolism; Intestinal Mucosa - metabolism; Intestines - microbiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - metabolism; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - immunology; Signal Transduction; Spotlight; Stromal Cells - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00670-15

Attaching and effacing pathogens, including enterohemorrhagic Escherichia coli in humans and Citrobacter rodentium in mice, raise serious public health concerns. Here we demonstrate that interleukin-1 receptor (IL-1R) signaling is indispensable for protection against C. rodentium infection in mice. Four days after infection with C. rodentium, there were significantly fewer neutrophils (CD11b+ Ly6C+ Ly6G+) in the colons of IL-1R−/− mice than in wild-type mice. Levels of mRNA and protein of KC/CXCL1 were also significantly reduced in colon homogenates of infected IL-1R−/− mice relative to wild-type mice. Of note, infiltrated CD11b+ Ly6C+ Ly6G+ neutrophils were the main source of IL-22 secretion after C. rodentium infection. Interestingly, intestinal stromal cells isolated from IL-1R−/− mice secreted lower levels of KC/CXCL1 than stromal cells from wild-type mice during C. rodentium infection. Similar effects were found when mouse intestinal stromal cells and human nasal polyp stromal cells were treated with IL-1R antagonists (i.e., anakinra) in vitro. These results suggest that IL-1 signaling plays a pivotal role in activating mucosal stromal cells to secrete KC/CXCL1, which is essential for infiltration of IL-22-secreting neutrophils upon bacterial infection.