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Role of SNARE proteins in the pathogenesis of HIV
Author(s) -
Achuthan Adrian,
Zhou Jing Ling,
Crowe Suzanne,
Jaworowski Anthony
Publication year - 2010
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.24.1_supplement.853.1
Subject(s) - biology , cd14 , secretion , effector , macrophage , phagocytosis , autophagy , immune system , intracellular , intracellular parasite , microbiology and biotechnology , rab , immunology , virology , apoptosis , gtpase , biochemistry , in vitro
Tuberculosis (TB) is the leading cause of death among HIV‐positive individuals. Indeed, HIV and M. tuberculosis (Mtb) co‐infected individuals have a 10% annual risk of reactivating latent Mtb infection. Macrophages are both the host cell for Mtb infection and also the cell directly responsible for Mtb killing. Hence, evasion of macrophage intracellular destruction mechanisms is pivotal to Mtb virulence. IFNγ promotes macrophage immune functions (e.g. cytokine secretion and phagocytosis) relevant to Mtb killing and immunity, in part by modulating expression and/or function of effector proteins (e.g. SNARE, autophagy and Rab proteins), controlling membrane vesicle fusion events. We report here that IFNγ‐induced STAT1 phosphorylation is impaired in HIV‐1‐infected primary human monocyte‐derived macrophages. We found IFNγ up‐regulates the expression of SNARE proteins Stx11 and VAMP8 in macrophages. Significantly, CD14+ monocytes from HIV‐1‐infected individuals displayed decreased protein levels of VAMP8 and Stx11 as compared to controls. The effects of IFNγ‐inducible Stx11 and VAMP8 on secreting cytokines and killing Mtb in macrophages will be presented and discussed.