Rcg. Pollok et al., Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum, GASTROENTY, 120(1), 2001, pp. 99-107
Background & Aims: Interferon (IFN)-gamma plays an important role in the im
munologic control of infection by the protozoan enteropathogen Cryptosporid
ium parvum. We tested the hypothesis that IFN-gamma may directly inhibit in
fection of enterocytes by this pathogen. Methods: HT-29, Caco-2, and H4 hum
an enterocyte cell lines were drown in monolayers and incubated with IFN-ga
mma before exposure with C. parvum. IFN-gamma receptor expression in the ce
ll lines was determined by Western blot analysis. Results: IFN-gamma inhibi
ted C. parvum infection of both HT-29 and Caco-2 cells but not H4 cells. Re
sponse to IFN-gamma, was related to the expression of the IFN-gamma recepto
r in the respective cell lines. The effect of IFN-gamma was partially rever
sed 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 Fe2+ concentration. No role for tryptop
han starvation or nitric oxide synthase activity was found. TNF-alpha and I
L-1 beta also had anti-C. parvum activity but had no synergistic effect wit
h IFN-gamma, Conclusions: IFN-gamma directly induces enterocyte resistance
against C parvum infection; this observation may have important consequence
s for our understanding of the mucosal immune response to invasive pathogen
s.