title: Microparticles released from Mycobacterium tuberculosis-infected human macrophages contain increased levels of the type I interferon inducible proteins including ISG15.
abstract: Microparticles (MPs) are small membranous particles (100-1000 nm) released under normal steady-state conditions and are thought to provide a communication network between host cells. Previous studies demonstrated that Mycobacterium tuberculosis (M. tb) infection of macrophages increased the release of MPs, and these MPs induced a proinflammatory response from uninfected macrophages in vitro and in vivo following their transfer into uninfected mice. To determine how M. tb infection modulates the protein composition of the MPs, and if this contributes to their proinflammatory properties, we compared the proteomes of MPs derived from M. tb-infected (TBinf-MP) and uninfected human THP-1 monocytic cells. MP proteins were analyzed by GeLC-MS/MS with spectral counting revealing 68 proteins with statistically significant differential abundances. The 42 proteins increased in abundance in TBinf-MPs included proteins associated with immune function (7), lysosomal/endosomal maturation (4), vesicular formation (12), nucleosome proteins (4), and antigen processing (9). Prominent among these were the type I interferon inducible proteins, ISG15, IFIT1, IFIT2, and IFIT3. Exposure of uninfected THP-1 cells to TBinf-MPs induced increased gene expression of isg15, ifit1, ifit2, and ifit3 and the release of proinflammatory cytokines. These proteins may regulate the proinflammatory potential of the MPs and provide candidate biomarkers for M. tb infection.
authors.affiliation: Tuberculosis Research Program, Centenary Institute, Disciplines of Medicine, Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, NSW, Australia.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Hare
authors.affiliation: Tuberculosis Research Program, Centenary Institute, Disciplines of Medicine, Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, NSW, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Chan
authors.affiliation: Tuberculosis Research Program, Centenary Institute, Disciplines of Medicine, Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, NSW, Australia.
authors.forename: Edwina
authors.initials: E
authors.lastname: Chan
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Kimberley L
authors.initials: KL
authors.lastname: Kaufman
authors.affiliation: Tuberculosis Research Program, Centenary Institute, Disciplines of Medicine, Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, NSW, Australia.
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.affiliation: Tuberculosis Research Program, Centenary Institute, Disciplines of Medicine, Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, NSW, Australia.|School of Life Sciences, University of Technology, Sydney, NSW, Australia.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Saunders
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line / Q000382:microbiology; D055252:Cell-Derived Microparticles / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D053719:Tandem Mass Spectrometry; D014376:Tuberculosis / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D016207:Cytokines; C484290:IFIT1 protein, human; C484289:IFIT2 protein, human; C116468:IFIT3 protein, human; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D014452:Ubiquitins; C074034:ISG15 protein, human
keywords: Macrophage; Microbiology; Microparticle; Mycobacterium tuberculosis