Alimentary TractInterferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum☆,☆☆
Section snippets
Reagents
All cytokines were purchased in lyophilized form and reconstituted according to supplier's instructions. Recombinant human IFN-γ was supplied by Sigma Ltd. (Poole, England), and TNF-α, IL-1β, and anti–IFN-γR α-chain antibody were obtained from R&D systems (Abingdon, England). The JAK 2 inhibitor, tyrphostin B42 (N-benzyl-3,4-dihydroxybenzylidenecyanoacetamide), and the selective iNOS inhibitor, 1400 W (N-[3-(aminomethyl)benzyl]acetamadine), were supplied by Calbiochem (Nottingham, England).
IFN-γ inhibits C. parvum development
IFN-γ was found to have a marked inhibitory effect on infection of HT-29 cell; for example, in cells exposed to 100 U/mL IFN-γ for 24 hours before parasite inoculation, there was a 73.8% ± 4.8% inhibition of parasite development (P < 0.001; Table 1).The level of inhibition was dependent on the exposure time of HT-29 cells to IFN-γ, with highest levels of inhibition being obtained after 24–72 hours of exposure of cells to IFN-γ before parasite inoculation (data not shown). Experiments were
Discussion
Our findings indicate for the first time mechanisms by which IFN-γ mediates its inhibitory action in the control of C. parvum infection in intestinal epithelial cells. Using an in vitro model of infection we have demonstrated a direct inhibitory action of IFN-γ on C. parvum–infected human enterocytes independent of cell-to-cell interactions with other mucosal immune effector cells. The inhibitory effect of IFN-γ against C. parvum infection is dependent on both the concentration of cytokine
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2021, ImmunityCitation Excerpt :Therefore, in contrast to other Ct strains (Ren et al., 2012; Sateriale et al., 2019), Ct-STL acts less like a pathogen and more like a commensal. IFN-γ signaling is important in the control of Cp in mice (Chen et al., 1993b; Pollok et al., 2001; Tessema et al., 2009). Consistent with these observations, we found that anti-IFN-γ antibody treatment increased Ct-STL oocyst shedding by 2 weeks, an effect also seen with Cp (Chen et al., 1993a) (Figure S3A).
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Address requests for reprints to: Richard C. G. Pollok, M. D., Digestive Diseases Research Centre and Department of Paediatric Gastroenterology, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, England. e-mail: [email protected]; fax: (44) 20-7882-7192.
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Supported by a grant from the Wellcome Trust Research Training Fellow (to R.C.G.P.) and partly funded by a Wellcome Trust project grant (to M.B.-E. and V.M).