Journal article

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, Dario S Zamboni

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2015

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. pneumo..

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University of Melbourne Researchers

Grants

Awarded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)


Awarded by Nucleo de Apoio a Pesquisa em Doencas Inflamatorias (NAPDIN)


Awarded by Science Without Borders Program (CNPq)


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This paper is dedicated to Dr Michel Rabinovitch, whose passion for biology and scientific investigation co-infects his students forever. We thank Maira Nakamura for her technical assistance, to Richard Flavell (Yale, USA) for providing us with Nlrc4<SUP>-/-</SUP> and Casp1/11<SUP>-/-</SUP> mice and Vishva Dixit (Genentech, USA) for providing us with Nlrp3<SUP>-/-</SUP>, Casp1<SUP>-/-</SUP>/Casp11<SUP>Tg</SUP> and Casp11<SUP>-/-</SUP> and the antibody to caspase-1 p20. This work was supported by grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, grants 2013/08216-2, 2014/50268-2 and 2014/04684-4), Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq and INCTV/CNPq), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Nucleo de Apoio a Pesquisa em Doencas Inflamatorias (NAPDIN, grant 11.1.21625.01.0) and the PEW Program in Biomedical Sciences. L.D.C. and J.M.R. are supported by fellowships from FAPESP. L.M.M. and T.D.F. are supported by fellowships from CAPES. H.J.N. is a visiting professor from Science Without Borders Program (CNPq, grant 401577/2014-7). D.S.Z. is a research fellow from CNPq, Brazil.