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

Larissa D. Cunha, Juliana M. Ribeiro, Talita D. Fernandes, Liliana M. Massis, Chen Ai Khoo, Jennifer H. Moffatt, Hayley J. Newton, Craig R. Roy and Dario S. Zamboni ()
Additional contact information
Larissa D. Cunha: Medical School of Ribeirão Preto, University of São Paulo (FMRP/USP)
Juliana M. Ribeiro: Medical School of Ribeirão Preto, University of São Paulo (FMRP/USP)
Talita D. Fernandes: Medical School of Ribeirão Preto, University of São Paulo (FMRP/USP)
Liliana M. Massis: Medical School of Ribeirão Preto, University of São Paulo (FMRP/USP)
Chen Ai Khoo: University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Jennifer H. Moffatt: University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Hayley J. Newton: University of Melbourne at the Peter Doherty Institute for Infection and Immunity
Craig R. Roy: Yale University School of Medicine
Dario S. Zamboni: Medical School of Ribeirão Preto, University of São Paulo (FMRP/USP)

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms10205 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10205

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10205

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().