1. Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein.
- Author
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Burette M, Allombert J, Lambou K, Maarifi G, Nisole S, Di Russo Case E, Blanchet FP, Hassen-Khodja C, Cabantous S, Samuel J, Martinez E, and Bonazzi M
- Subjects
- Animals, Bacterial Proteins genetics, Coxiella burnetii genetics, Female, Host-Pathogen Interactions, Humans, Immunity, Innate, Mice, Mice, Inbred C57BL, Mice, SCID, Q Fever genetics, Q Fever microbiology, Bacterial Proteins metabolism, Coxiella burnetii metabolism, Q Fever immunology
- Abstract
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., Competing Interests: The authors declare no competing interest.
- Published
- 2020
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