title: 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.
abstract: 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.
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Yang
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Yeji
authors.initials: Y
authors.lastname: Kim
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji Heui
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Ju
authors.initials: YJ
authors.lastname: Jang
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D044082:Citrobacter rodentium / Q000502:physiology*; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D054360:Chemokine CXCL1; D007375:Interleukin-1; D007378:Interleukins; D017472:Receptors, Interleukin-1; D000097043:Interleukin-22; C475895:Cxcl1 protein, mouse