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IL‐23 aids in defense against Francisella infection
Author(s) -
Butchar Jonathan P.,
Rajaram Murugesan V.S.,
Parsa Kishore V.L.,
Clay Corey D.,
Gunn John S.,
Schlesinger Larry S.,
Tridandapani Susheela
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.675.14
Subject(s) - francisella tularensis , tularemia , francisella , virulence , biology , microbiology and biotechnology , virology , immunology , gene , biochemistry
Francisella tularensis is the causative agent of tularemia and is classified as a Category A bioterrorism threat. It primarily invades monocytes and macrophages, where it escapes the phagosome and replicates in the cytosol. We performed a microarray screen to study human monocyte responses to F. tularensis novicida , a related subspecies lethal to mice. We identified IL‐23, a recently discovered cytokine related to IL‐12, and confirmed its upregulation using Western blotting and ELISAs. Functional studies showed that this infection‐induced IL‐23 could elicit IFNg production in natural killer cells. Hence, IL‐23 is important during infection, since IFNg is needed for IL‐12 production and blockage of both IL‐23 and IL‐12 leads to higher infectivity. Monocyte infection with virulent Francisella (SCHU S4) also led to IL‐23 production, but at much lower levels than from F. novicida . Further studies showed that IL‐23 production requires PI3 Kinase and NFkB activation, which are negatively regulated by the inositol phosphatase SHIP. Interestingly, SHIP was downregulated by F. novicida but not by SCHU S4 infection. This may account for the reduced IL‐23 response to the more virulent strain.