Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein. Academic Article uri icon

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.

published proceedings

  • Proc Natl Acad Sci U S A

author list (cited authors)

  • Burette, M., Allombert, J., Lambou, K., Maarifi, G., Nisole, S., Di Russo Case, E., ... Bonazzi, M.

complete list of authors

  • Burette, Melanie||Allombert, Julie||Lambou, Karine||Maarifi, Ghizlane||Nisole, S├ębastien||Di Russo Case, Elizabeth||Blanchet, Fabien P||Hassen-Khodja, Cedric||Cabantous, St├ęphanie||Samuel, James||Martinez, Eric||Bonazzi, Matteo

publication date

  • June 2020