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Microparticles released from Mycobacterium tuberculosis ‐infected human macrophages contain increased levels of the type I interferon inducible proteins including ISG15
Author(s) -
Hare Nathan J.,
Chan Brian,
Chan Edwina,
Kaufman Kimberley L.,
Britton Warwick J.,
Saunders Bernadette M.
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400610
Subject(s) - proinflammatory cytokine , isg15 , immune system , proteome , biology , mycobacterium tuberculosis , immunology , chemistry , microbiology and biotechnology , inflammation , tuberculosis , medicine , gene , biochemistry , pathology , ubiquitin
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.