Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA

72Citations
Citations of this article
94Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Coxiella burnetii is a highly infectious bacterium that promotes its own replication in macrophages by inhibiting several host cell responses. Here, we show that C. burnetii inhibits caspase-1 activation in primary mouse macrophages. By using co-infection experiments, we determine that the infection of macrophages with C. burnetii inhibits the caspase-11-mediated non-canonical activation of the NLRP3 inflammasome induced by subsequent infection with Escherichia coli or Legionella pneumophila. Genetic screening using flagellin mutants of L. pneumophila as a surrogate host, reveals a novel C. burnetii gene (IcaA) involved in the inhibition of caspase activation. Expression of IcaA in L. pneumophila inhibited the caspase-11 activation in macrophages. Moreover, icaA-mutants of C. burnetii failed to suppress the caspase-11-mediated inflammasome activation induced by L. pneumophila. Our data reveal IcaA as a novel C. burnetii effector protein that is secreted by the Dot/Icm type IV secretion system and interferes with the caspase-11-induced, non-canonical activation of the inflammasome.

Cite

CITATION STYLE

APA

Cunha, L. D., Ribeiro, J. M., Fernandes, T. D., Massis, L. M., Khoo, C. A., Moffatt, J. H., … Zamboni, D. S. (2015). Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA. Nature Communications, 6. https://doi.org/10.1038/ncomms10205

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free