Dysregulation of interferon-gamma-mediated signalling pathway in intestinal epithelial cells by Cryptosporidium parvum infection.
The apicomplexan parasite Cryptosporidium parvum, the agent of cryptosporidiosis, primarily infects and reproduces in enterocytes. Interferon (IFN)-gamma is important for early control of the infection and acts directly on enterocytes to inhibit parasite development, although complete inhibition is not obtained. Addressing this latter observation, an investigation was made of the modulatory effect of C. parvum infection on IFN-gamma-dependent enterocyte gene expression. Initial studies showed that IFN-gamma-induced expression of indoleamine 2, 3 dioxygenase (IDO) mRNA and protein in CMT-93 cells was abrogated by C. parvum infection. Infection also inhibited IDO expression by the human enterocyte cell lines HT29 and Caco-2. Expression of IFN-gamma-inducible genes important in the development of immune responses, including major histocompatibility complex class II and CIITA, was also inhibited by the parasite. Investigating a possible mechanism for these findings, it was shown that infection caused depletion of STAT1alpha protein, a key transcription factor in IFN-gamma signalling. These findings indicate C. parvum interferes with IFN-gamma-dependent gene expression in enterocytes and suggest this activity could be a novel immuno-evasive strategy employed by the parasite.
Choudhry
Naheed
N
Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Institute of Cell and Molecular Science, Centre for Gastroenterology, London, UK.
Korbel
Daniel S
DS
Edwards
Lyndsey A
LA
Bajaj-Elliott
Mona
M
McDonald
Vincent
V
D000818:Animals; D002460:Cell Line; D016785:Cryptosporidium parvum / Q000276:immunology*; D020895:Enterocytes / Q000276:immunology* / Q000469:parasitology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction
D050832:Interferon-Stimulated Gene Factor 3; C079868:gamma interferon activation factor; D007371:Interferon-gamma