Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma

Illya Tietzel; Christelle El-Haibi; Rey A Carabeo

doi:10.1371/journal.pone.0006499

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Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma

Journal article

Open access

Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma

Illya Tietzel, Christelle El-Haibi and Rey A Carabeo

PloS one, Vol.4(8), pp.e6499-e6499

08/04/2009

DOI: https://doi.org/10.1371/journal.pone.0006499

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https://hdl.handle.net/2376/106032

PMCID: PMC2714978

PMID: 19652711

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Abstract

GTP-Binding Proteins - physiology

Humans

Interferon-gamma - physiology

DNA Primers

Gene Knockdown Techniques

Chlamydia trachomatis - growth & development

Base Sequence

Chlamydia trachomatis - pathogenicity

Polymerase Chain Reaction

RNA, Small Interfering

HeLa Cells

Intracellular Membranes - metabolism

Microscopy, Fluorescence

GTP-Binding Proteins - metabolism

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.

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Title: Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma
Creators: Illya Tietzel - Department of Natural Sciences, Southern University of New Orleans, New Orleans, LA, USA
Christelle El-Haibi
Rey A Carabeo
Publication Details: PloS one, Vol.4(8), pp.e6499-e6499
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 AI065545-02 / NIAID NIH HHS R01 AI065545 / NIAID NIH HHS AI065545 / NIAID NIH HHS K22 AI052252 / NIAID NIH HHS AI052252 / NIAID NIH HHS
Identifiers: 99900546850901842
Language: English
Resource Type: Journal article