Rapid dendritic cell mobilization to the large intestinal epithelium is associated with resistance to Trichuris muris infection

Sheena M. Cruickshank, Matthew L. Deschoolmeester, Marcus Svensson, Gareth Howell, Aikaterini Bazakou, Larisa Logunova, Matthew C. Little, Nicholas English, Matthias Mack, Richard K. Grencis, Kathryn J. Else, Simon R. Carding

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

The large intestine is a major site of infection and disease, yet little is known about how immunity is initiated within this site and the role of dendritic cells (DCs) in this process. We used the well-established model of Trichuris muris infection to investigate the innate response of colonic DCs in mice that are inherently resistant or susceptible to infection. One day postinfection, there was a significant increase in the number of immature colonic DCs in resistant but not susceptible mice. This increase was sustained at day 7 postinfection in resistant mice when the majority of the DCs were mature. There was no increase in DC numbers in susceptible mice until day 13 postinfection. In resistant mice, most colonic DCs were located in or adjacent to the epithelium postinfection. There were also marked differences in the expression of colonic epithelial chemokines in resistant mice and susceptible mice. Resistant mice had significantly increased levels of epithelium-derived CCL2, CCL3, CCL5, and CCL20 compared with susceptible mice. Furthermore, administering neutralizing CCL5 and CCL20 Abs to resistant mice prevented DC recruitment. This study provides clear evidence of differences in the kinetics of DC responses in hosts inherently resistant and susceptible to infection. DC responses in the colon correlate with resistance to infection. Differences in the production of DC chemotactic chemokines by colonic epithelial cells in response to infection in resistant vs susceptible mice may explain the different kinetics of the DC response.
Original languageEnglish
Pages (from-to)3055-3062
Number of pages8
JournalJournal of Immunology
Volume182
Issue number5
DOIs
Publication statusPublished - 2009

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