human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-γ人类鸟苷结合蛋白加强anti-chlamydia interferon-γ的影响.pdfVIP

Human Guanylate Binding Proteins Potentiate the Anti- Chlamydia Effects of Interferon-c 1 2 3 Illya Tietzel , Christelle El-Haibi , Rey A. Carabeo * 1 Department of Natural Sciences, Southern University of New Orleans, New Orleans, Louisiana, United States of America, 2 Department of Microbiology and Immunology, University of Louisville Medical School, Louisville, Kentucky, United States of America, 3 Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom Abstract Chlamydiae are obligate intracellular pathogens that are sensitive to pro-inflammatory cytokine interferon-c. IFN-c-inducible murine p47 GTPases have been demonstrated to function in resistance to chlamydia infection in vivo and in vitro. Because the human genome does not encode IFN-c-inducible homologues of these proteins, the significance of the p47 GTPase findings to chlamydia pathogenesis in humans is unclear. Here we report a pair of IFN-c-inducible proteins, the human guanylate binding proteins (hGBPs) 1 and 2 that potentiate the anti-chlamydial properties of IFN-c. hGBP1 and 2 localize to the inclusion membrane, and their anti-chlamydial functions required the GTPase domain. Alone, hGBP1 or 2 have mild, but statistically significant and reproducible negative effects on the growth of Chlamydia trachomatis, whilst having potent anti- chlamydial activity in conjunction with treatment with a sub-inhibitory concentration of IFN-c. Thus, hGBPs appear to potentiate the anti-chlamydial effects of IFN-c. Indeed, depletion of hGBP1 and 2 in cells treated with IFN-c led to an increase in inclusion size, indicative of better growth. Interestingly, chlamydia species/strains harboring the full-length version of the p