%0 Journal Article
%T Human Guanylate Binding Proteins Potentiate the Anti-Chlamydia Effects of Interferon-¦Ã
%A Illya Tietzel
%A Christelle El-Haibi
%A Rey A. Carabeo
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0006499
%X Chlamydiae are obligate intracellular pathogens that are sensitive to pro-inflammatory cytokine interferon-¦Ã. IFN-¦Ã-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-¦Ã-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-¦Ã-inducible proteins, the human guanylate binding proteins (hGBPs) 1 and 2 that potentiate the anti-chlamydial properties of IFN-¦Ã. 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-¦Ã. Thus, hGBPs appear to potentiate the anti-chlamydial effects of IFN-¦Ã. Indeed, depletion of hGBP1 and 2 in cells treated with IFN-¦Ã led to an increase in inclusion size, indicative of better growth. Interestingly, chlamydia species/strains harboring the full-length version of the putative cytotoxin gene, which has been suggested to confer resistance to IFN-¦Ã was not affected by hGBP overexpression. These findings identify the guanylate binding proteins as potentiators of IFN-¦Ã inhibition of C. trachomatis growth, and may be the targets of the chlamydial cytotoxin.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006499