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Gastroenterology. 2001 Jan;120(1):99-107.

Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum.

Author information

1
Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London, England. r.c.pollok@mds.qmw.ac.uk

Abstract

BACKGROUND & AIMS:

Interferon (IFN)-gamma plays an important role in the immunologic control of infection by the protozoan enteropathogen Cryptosporidium parvum. We tested the hypothesis that IFN-gamma may directly inhibit infection of enterocytes by this pathogen.

METHODS:

HT-29, Caco-2, and H4 human enterocyte cell lines were grown in monolayers and incubated with IFN-gamma before exposure with C. parvum. IFN-gamma receptor expression in the cell lines was determined by Western blot analysis.

RESULTS:

IFN-gamma inhibited C. parvum infection of both HT-29 and Caco-2 cells but not H4 cells. Response to IFN-gamma was related to the expression of the IFN-gamma receptor in the respective cell lines. The effect of IFN-gamma was partially reversed by inhibition of the JAK/STAT signaling pathway. IFN-gamma mediated its action by at least 2 mechanisms: (1) inhibition of parasite invasion and (2) by modification of intracellular Fe(2+) concentration. No role for tryptophan starvation or nitric oxide synthase activity was found. TNF-alpha and IL-1beta also had anti-C. parvum activity but had no synergistic effect with IFN-gamma.

CONCLUSIONS:

IFN-gamma directly induces enterocyte resistance against C. parvum infection; this observation may have important consequences for our understanding of the mucosal immune response to invasive pathogens.

PMID:
11208718
[Indexed for MEDLINE]
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