Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma.
Chlamydiae are obligate intracellular pathogens that are sensitive to pro-inflammatory cytokine interferon-gamma. IFN-gamma-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-gamma-in...
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Public Library of Science (PLoS)
2009-08-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006499&type=printable |
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| author | Illya Tietzel Christelle El-Haibi Rey A Carabeo |
| author_facet | Illya Tietzel Christelle El-Haibi Rey A Carabeo |
| author_sort | Illya Tietzel |
| collection | DOAJ |
| description | Chlamydiae are obligate intracellular pathogens that are sensitive to pro-inflammatory cytokine interferon-gamma. IFN-gamma-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-gamma-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-gamma-inducible proteins, the human guanylate binding proteins (hGBPs) 1 and 2 that potentiate the anti-chlamydial properties of IFN-gamma. 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-gamma. Thus, hGBPs appear to potentiate the anti-chlamydial effects of IFN-gamma. Indeed, depletion of hGBP1 and 2 in cells treated with IFN-gamma 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-gamma was not affected by hGBP overexpression. These findings identify the guanylate binding proteins as potentiators of IFN-gamma inhibition of C. trachomatis growth, and may be the targets of the chlamydial cytotoxin. |
| format | Article |
| id | doaj-art-be2785c89c354e768e23eccf8d29254d |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-be2785c89c354e768e23eccf8d29254d2025-08-20T02:00:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-08-0148e649910.1371/journal.pone.0006499Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma.Illya TietzelChristelle El-HaibiRey A CarabeoChlamydiae are obligate intracellular pathogens that are sensitive to pro-inflammatory cytokine interferon-gamma. IFN-gamma-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-gamma-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-gamma-inducible proteins, the human guanylate binding proteins (hGBPs) 1 and 2 that potentiate the anti-chlamydial properties of IFN-gamma. 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-gamma. Thus, hGBPs appear to potentiate the anti-chlamydial effects of IFN-gamma. Indeed, depletion of hGBP1 and 2 in cells treated with IFN-gamma 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-gamma was not affected by hGBP overexpression. These findings identify the guanylate binding proteins as potentiators of IFN-gamma inhibition of C. trachomatis growth, and may be the targets of the chlamydial cytotoxin.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006499&type=printable |
| spellingShingle | Illya Tietzel Christelle El-Haibi Rey A Carabeo Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. PLoS ONE |
| title | Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. |
| title_full | Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. |
| title_fullStr | Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. |
| title_full_unstemmed | Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. |
| title_short | Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. |
| title_sort | human guanylate binding proteins potentiate the anti chlamydia effects of interferon gamma |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0006499&type=printable |
| work_keys_str_mv | AT illyatietzel humanguanylatebindingproteinspotentiatetheantichlamydiaeffectsofinterferongamma AT christelleelhaibi humanguanylatebindingproteinspotentiatetheantichlamydiaeffectsofinterferongamma AT reyacarabeo humanguanylatebindingproteinspotentiatetheantichlamydiaeffectsofinterferongamma |