Mast cells disrupt epithelial barrier function during enteric nematode infection

Jacqueline R. McDermott, Ruth E. Bartram, Pamela A. Knight, Hugh R P Miller, David R. Garrod, Richard K. Grencis

    Research output: Contribution to journalArticlepeer-review


    We have investigated the influence of mast cells on the barrier function of intestinal epithelium during nematode infection. Trichinella spiralis infection induces a strong type 2 cytokine-mediated inflammation, resulting in a critical mucosal mastocytosis that is known to mediate expulsion of the parasites from the intestine. The host response to infection is also characterized by an increase in mucosal leakiness. We show here that intestinal epithelial permeability is markedly elevated during infection, with kinetics that mirror the adaptive immune response to primary and secondary infection. Furthermore, we have identified degradation of the tight junction protein, occludin, thereby providing a mechanism for increased paracellular permeability during helminth infection. We further demonstrate by using anti-c-kit antibody and IL-9 transgenic mice that mast cells are directly responsible for increasing epithelial paracellular permeability and that mice deficient in a mast cell-specific protease fail to increase intestinal permeability and fail to expel their parasite burden. These results provide the mechanism whereby mucosal mast cells mediate parasite expulsion from the intestine.
    Original languageEnglish
    Pages (from-to)7761-7766
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number13
    Publication statusPublished - 24 Jun 2003


    Dive into the research topics of 'Mast cells disrupt epithelial barrier function during enteric nematode infection'. Together they form a unique fingerprint.

    Cite this