Cutting Edge: Mutation of Francisella tularensis mviN Leads to Increased Macrophage Absent in Melanoma 2 Inflammasome Activation and a Loss of Virulence

Tyler K Ulland; Blake W Buchan; Margaret R Ketterer; Teresa Fernandes-Alnemri; David K Meyerholz; Michael A Apicella; Emad S Alnemri; Bradley D Jones; William M Nauseef; Fayyaz S Sutterwala

doi:10.4049/jimmunol.1001610

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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

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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

Tyler K Ulland, Blake W Buchan, Margaret R Ketterer, Teresa Fernandes-Alnemri, David K Meyerholz, Michael A Apicella, Emad S Alnemri, Bradley D Jones, William M Nauseef and Fayyaz S Sutterwala

The Journal of immunology (1950), Vol.185(5), pp.2670-2674

09/01/2010

DOI: 10.4049/jimmunol.1001610

PMCID: PMC2953561

PMID: 20679532

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Abstract

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 AIM2 inflammasome-dependent IL-1β secretion and cytotoxicity in macrophages. The compromised in vivo virulence of the mviN mutant depended upon inflammasome activation, as caspase-1- and ASC-deficient mice did not exhibit preferential survival following infection. This study demonstrates that mviN limits F. tularensis -induced AIM2 inflammasome activation which is critical for its virulence in vivo .

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Title: Subtitle: Cutting Edge: Mutation of Francisella tularensis mviN Leads to Increased Macrophage Absent in Melanoma 2 Inflammasome Activation and a Loss of Virulence
Creators: Tyler K Ulland - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Blake W Buchan - Department of Microbiology, University of Iowa, Iowa City, IA 52242
Margaret R Ketterer - Department of Microbiology, University of Iowa, Iowa City, IA 52242
Teresa Fernandes-Alnemri - Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA 52242
Michael A Apicella - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Emad S Alnemri - Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107
Bradley D Jones - Department of Microbiology, University of Iowa, Iowa City, IA 52242
William M Nauseef - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Fayyaz S Sutterwala - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.185(5), pp.2670-2674
DOI: 10.4049/jimmunol.1001610
PMID: 20679532
PMCID: PMC2953561
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Language: English
Date published: 09/01/2010
Academic Unit: Microbiology and Immunology; Infectious Diseases; Pathology; Internal Medicine
Record Identifier: 9984083899902771

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