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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2020

Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein

Cedric Hassen-Khodja

Résumé

The Q fever agent Coxiella burnetii uses a defect in organelle trafficking/intracellular multiplication (Dot/Icm) type 4b secretion system (T4SS) to silence the host innate immune response during infection. By investigating C. burnetii effector proteins containing eukaryotic-like domains, here we identify NopA (nucleolar protein A), which displays four regulator of chromosome condensation (RCC) repeats, homologous to those found in the eukaryotic Ras-related nuclear protein (Ran) guanine nucleotide exchange factor (GEF) RCC1. Accordingly, NopA is found associated with the chromatin nuclear fraction of cells and uses the RCC-like domain to interact with Ran. Interestingly, NopA triggers an accumulation of Ran-GTP, which accumulates at nucleoli of transfected or infected cells, thus perturbing the nuclear import of transcription factors of the innate immune signaling pathway. Accordingly, qRT-PCR analysis on a panel of cytokines shows that cells exposed to the C. burnetii nopA::Tn or a Dot/Icm-defective dotA::Tn mutant strain present a functional innate immune response, as opposed to cells exposed to wild-type C. burnetii or the corresponding nopA complemented strain. Thus, NopA is an important regulator of the innate immune response allowing Coxiella to behave as a stealth pathogen.
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Dates et versions

hal-02874541 , version 1 (06-11-2020)

Identifiants

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Melanie Burette, Julie Allombert, Karine Lambou, Ghizlane Maarifi, Sébastien Nisole, et al.. Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (24), pp.13708-13718. ⟨10.1073/pnas.1914892117⟩. ⟨hal-02874541⟩
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