GM-CSF-Facilitated Dendritic Cell Recruitment and Survival Govern the Intestinal Mucosal Response to a Mouse Enteric Bacterial Pathogen

Yoshihiro Hirata, Laia Egea, Sara Dann-Grice, Lars Eckmann, Martin F. Kagnoff

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)151-163
Number of pages13
JournalCell Host and Microbe
Volume7
Issue number2
DOIs
StatePublished - Feb 18 2010
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor
Dendritic Cells
Cell Survival
Intestinal Mucosa
Citrobacter rodentium
Wild Animals
Chemotactic Factors
Infection
Antibody Formation
Cell Differentiation
Up-Regulation
Cell Count
Epithelial Cells
Inflammation

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

GM-CSF-Facilitated Dendritic Cell Recruitment and Survival Govern the Intestinal Mucosal Response to a Mouse Enteric Bacterial Pathogen. / Hirata, Yoshihiro; Egea, Laia; Dann-Grice, Sara; Eckmann, Lars; Kagnoff, Martin F.

In: Cell Host and Microbe, Vol. 7, No. 2, 18.02.2010, p. 151-163.

Research output: Contribution to journalArticle

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