Abstract
Chlamydia, the most common sexually transmitted pathogen, is an exquisitely adapted Gram-negative obligate intracellular bacterium. Intracellular Chlamydia trachomatis replicate in a specialized vacuole, termed inclusion, which shields the bacterium from antimicrobial immunity of the host cells and acts as a signalling interface. Previously it was shown that members of the interferon induced guanylate binding protein (mGBP) family, in particular murine GBP1 and mGBP2, were found to accumulate at the bacterial inclusions, similar to previously published recruitment of GBPs to the parasitophorous vacuole of Toxoplasma gondii. Here, we provide a wide comparison of mGBPs roles within the host cell in the context of Chlamydia and Toxoplasma infection. By confocal microscopy on fixed and living infected cells we show localization of mGBP3, mGBP6, mGBP7, mGBP9, and mGBP10, in addition to mGBP1 and mGBP2, at chlamydia inclusions. In time lapse videos using GFP expressing Chlamydia we show rapid and transient dynamics of mGBP9 accumulation onto chlamydia inclusions. Taken together this study reveals a broad activation of mGBP recruitment towards Chlamydia trachomatis inclusions after infection and provides evidence for time limited action of mGBP9 at the chlamydia inclusion.
Highlights
The host response against intracellular pathogens is orchestrated by Interferon γ (IFNγ), an important pro-inflammatory cytokine which induces a wide range of genes, amongst which genes of the Guanylate Binding Proteins (GBPs) are very abundantly expressed [1,2,3]
MGBP1 and murine GBP2 (mGBP2) were found to locate to an intracellular pathogen compartment commonly referred to as ‘inclusion’ in C. trachomatis infected cells [30]
Based on homologies between mGBP sequences [4] and the ability of mGBPs to form multimers [11], we hypothesized that additional mGBPs might be involved in anti-bacterial resistance to C. trachomatis
Summary
The host response against intracellular pathogens is orchestrated by Interferon γ (IFNγ), an important pro-inflammatory cytokine which induces a wide range of genes, amongst which genes of the Guanylate Binding Proteins (GBPs) are very abundantly expressed [1,2,3]. Through GTP hydrolysis via GDP to GMP the GBPs have the ability to form multimers in vesicle like structures (VLS) and accumulate into supramolecular complexes around pathogen containing vacuoles [10,11,12,13,14,15]. It was shown by FRET-based interaction studies in living cells that murine GBP2 (mGBP2) multimerizes predominately with mGBP1 and mGBP3, but not with mGBP5 or mGBP6 [11]. Various immune functions of mGBPs in various effector pathways have been described, for example
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