Microparticles released from Mycobacterium tuberculosis‐infected human macrophages contain increased levels of the type I interferon inducible proteins including ISG15. Issue 17 (3rd July 2015)

• Record Type: Journal Article
• Authors: Hare, Nathan J.; Chan, Brian; Chan, Edwina; Kaufman, Kimberley L.; Britton, Warwick J.; Saunders, Bernadette M.
• Is Part Of: Proteomics. Volume 15:Issue 17(2015:Sep.)
• Page Start: 3020
• Page End: 3029
• Publication Date: 2015-07-03
• Subjects: Proteins -- Separation -- Periodicals; Bioinformatics -- Periodicals; Proteomics -- Periodicals; Genomes -- Periodicals; Molecular genetics -- Periodicals; 572.605
• DOI: 10.1002/pmic.201400610
• Languages: English
• ISSNs: 1615-9853

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Mycobacterium tuberculosis</italic> (<italic>M. tb</italic>) 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 <italic>M. tb</italic> infection modulates the protein composition of the MPs, and if this contributes to their proinflammatory properties, we compared the proteomes of MPs derived from <italic>M. tb</italic>‐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 <italic>isg15</italic>, <italic>ifit1</italic>, <italic>ifit2</italic>, and <italic>ifit3</italic> and the release of proinflammatory cytokines. These proteins may regulate the proinflammatory potential of the MPs and provide candidate biomarkers for <italic>M. tb</italic> infection.</p> </abstract>