GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes dendritic cell (DC) differentiation and survival in vitro. However, its role in host defense at the intestinal mucosa is unknown. We report that infection with the mouse enteric pathogen, Citrobacter rodentium, increased colonic GM-CSF production and CD11c(+) DC recruitment. After infection, GM-CSF(-/-) mice had fewer mucosal CD11c(+) DCs, greater bacterial burden, increased mucosal inflammation and systemic spread of infection, decreased antibody responses, and delayed pathogen clearance. This defective mucosal response was rescued by GM-CSF administration to GM-CSF(-/-) mice and mimicked by CD11c(+) DC depletion in wild-type animals. Diminished mucosal DC numbers in infected GM-CSF(-/-) mice reflected decreased DC recruitment and survival, with the recruitment defect being related to a failure to upregulate epithelial cell production of the DC chemoattractant, CCL22. Thus, GM-CSF produced in the intestinal mucosa acts to enhance host protection against an enteric bacterial pathogen through regulating recruitment and survival of DCs.
Department of Medicine, University of California, San Diego, La Jolla, 92093-0623, USA.
Yoshihiro
Y
Hirata
Laia
L
Egea
Sara M
SM
Dann
Lars
L
Eckmann
Martin F
MF
Kagnoff
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D044082:Citrobacter rodentium / Q000276:immunology*; D015169:Colony Count, Microbial; D003713:Dendritic Cells / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis
D000907:Antibodies, Bacterial; D016178:Granulocyte-Macrophage Colony-Stimulating Factor