Ulland TK, Buchan BW, Ketterer MR, Fernandes-Alnemri T, Meyerholz DK, Apicella MA, Alnemri ES, Jones BD, Nauseef WM, Sutterwala FS
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Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence.
J Immunol. 2010 Sep 1;185(5):2670-4
Authors: Ulland TK, Buchan BW, Ketterer MR, Fernandes-Alnemri T, Meyerholz DK, Apicella MA, Alnemri ES, Jones BD, Nauseef WM, Sutterwala FS
The mechanisms by which the intracellular pathogen Francisella tularensis evades innate immunity are not well defined. We have identified a gene with homology to Escherichia coli mviN, a putative lipid II flippase, which F. tularensis uses to evade activation of innate immune pathways. Infection of mice with a F. tularensis mviN mutant resulted in improved survival and decreased bacterial burdens compared to infection with wild-type F. tularensis. The mviN mutant also induced increased absent in melanoma 2 inflammasome-dependent IL-1beta secretion and cytotoxicity in macrophages. The compromised in vivo virulence of the mviN mutant depended upon inflammasome activation, as caspase 1- and apoptosis-associated speck-like protein containing a caspase recruitment domain-deficient mice did not exhibit preferential survival following infection. This study demonstrates that mviN limits F. tularensis-induced absent in melanoma 2 inflammasome activation, which is critical for its virulence in vivo.
PMID: 20679532 [PubMed - in process]
