title: Interleukin-27 inhibits phagosomal acidification by blocking vacuolar ATPases.
abstract: Interleukin (IL)-27 is a unique cytokine that has a dual role in immune responses. It was originally described to promote Th1 differentiation but also suppresses inflammation by inhibiting these and other inflammatory T cell subsets. Inhibition of inflammatory activity in macrophages has also been reported. These reports have largely focused on cytokine profiles or signaling mechanisms. To date, there have been no reports of how IL-27 may directly influence cellular mechanisms that operate to control microbial growth. Formation of a phagolysosome that acquires antimicrobial properties is an essential step for destruction of pathogens or pathogen-derived materials that are internalized by macrophages. Here we report that IL-27 has a profound influence on this critical innate immunity pathway. Treatment of human macrophages with IL-27 interferes with the acidification of phagosomes by reducing protein levels of V-ATPase and impairs control of bacterial pathogens.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, University of South Carolina, School of Medicine, Columbia, SC 29209, USA.
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Jung
authors.forename: Cory M
authors.initials: CM
authors.lastname: Robinson
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000276:immunology*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010588:Phagosomes / Q000502:physiology*; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D007378:Interleukins; C464565:MYDGF protein, human; D025262:Vacuolar Proton-Translocating ATPases
references.citation: Immunity. 2002 Jun;16(6):779-90
references.pmid: 12121660
references.citation: J Immunol. 2008 May 1;180(9):6325-33
references.pmid: 18424756
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1619-24
references.pmid: 22307620
references.citation: J Infect Dis. 2008 Aug 1;198(3):359-66
references.pmid: 18557702
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5437-42
references.pmid: 12702770
references.citation: Arch Biochem Biophys. 2008 Aug 1;476(1):33-42
references.pmid: 18406336
references.citation: J Biol Chem. 1997 Nov 21;272(47):29810-20
references.pmid: 9368053
references.citation: J Immunol. 2010 Jun 15;184(12):7071-81
references.pmid: 20483752
references.citation: Nat Rev Mol Cell Biol. 2009 Sep;10(9):623-35
references.pmid: 19672277
references.citation: J Immunol. 1999 Apr 15;162(8):4606-13
references.pmid: 10202000
references.citation: J Immunol. 2004 Dec 15;173(12):7490-6
references.pmid: 15585875
references.citation: J Leukoc Biol. 2009 Dec;86(6):1295-303
references.pmid: 19801497
references.citation: J Cell Sci. 1998 Apr;111 ( Pt 7):897-905
references.pmid: 9490634
references.citation: J Immunol. 2005 Mar 15;174(6):3534-44
references.pmid: 15749890
references.citation: Arch Immunol Ther Exp (Warsz). 2006 Jan-Feb;54(1):15-24
references.pmid: 16642253