title: Interleukin-7 produced by intestinal epithelial cells in response to Citrobacter rodentium infection plays a major role in innate immunity against this pathogen.
abstract: Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacterium Citrobacter rodentium. C. rodentium infection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response to C. rodentium was dependent on gamma interferon (IFN-γ)-producing NK1.1(+) cells and IL-12. Treatment with anti-IL-7Rα antibody during C. rodentium infection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity against C. rodentium during the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover, C. rodentium-induced expansion and activation of intestinal CD4(+) lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response to C. rodentium infection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Du
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China Junojin1@gmail.com.
authors.forename: Jun-O
authors.identifier: http://orcid.org/0000-0003-4216-8111
authors.initials: JO
authors.lastname: Jin
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000502:physiology*; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015851:Interleukin-7