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 01;185(5):2670-4
Date
08/04/2010Pubmed ID
20679532Pubmed Central ID
PMC2953561DOI
10.4049/jimmunol.1001610Scopus ID
2-s2.0-78049394393 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
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.
Author List
Ulland TK, Buchan BW, Ketterer MR, Fernandes-Alnemri T, Meyerholz DK, Apicella MA, Alnemri ES, Jones BD, Nauseef WM, Sutterwala FSAuthor
Blake W. Buchan PhD Professor in the Pathology and Laboratory Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBacterial Proteins
Bacterial Vaccines
Bone Marrow Cells
DNA-Binding Proteins
Down-Regulation
Francisella tularensis
Inflammation Mediators
Macrophage Activation
Macrophages
Melanoma
Mice
Mice, Knockout
Mutation
Nuclear Proteins
Up-Regulation
Virulence
Virulence Factors
