SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.
AuthorsBerger SB, Romero X, Ma C, Wang G, Faubion WA, Liao G, Compeer E, Keszei M, Rameh L, Wang N, Boes M, Regueiro JR, Reinecker HC, Terhorst C,
JournalNat Immunol
PubMed ID20818396
'Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of gram-negative bacteria by macrophages. ... More
Glucose-6-phosphatase-ß, implicated in a congenital neutropenia syndrome, is essential for macrophage energy homeostasis and functionality.
AuthorsJun HS, Cheung YY, Lee YM, Mansfield BC, Chou JY,
JournalBlood
PubMed ID22246029
'Glucose-6-phosphatase-ß (G6Pase-ß or G6PC3) deficiency, also known as severe congenital neutropenia syndrome 4, is characterized not only by neutropenia but also impaired neutrophil energy homeostasis and functionality. We now show the syndrome is also associated with macrophage dysfunction, with murine G6pc3(-/-) macrophages having impairments in their respiratory burst, chemotaxis, calcium ... More
Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocytes of choroideremia patients.
'BACKGROUND: Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and ... More
Cdc42 promotes host defenses against fatal infection.
The small Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, invasion, migration, differentiation, and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) ... More
SOCS3 deficiency promotes M1 macrophage polarization and inflammation.
AuthorsQin H, Holdbrooks AT, Liu Y, Reynolds SL, Yanagisawa LL, Benveniste EN,
JournalJ Immunol
PubMed ID22925925
Macrophages participate in both the amplification of inflammation at the time of injury and downregulation of the inflammatory response to avoid excess tissue damage. These divergent functions of macrophages are dictated by their microenvironment, especially cytokines, which promote a spectrum of macrophage phenotypes. The M1 proinflammatory phenotype is induced by ... More
HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy.
AuthorsHearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, Landay AL, Jaworowski A, Crowe SM,
JournalAIDS
PubMed ID22313961
OBJECTIVES:: To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals. DESIGN:: A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV-positive males aged 45 years or ... More
Development and validation of a flow cytometric method to evaluate phagocytosis of pHrodo™ BioParticles® by granulocytes in multiple species.
AuthorsNeaga A, Lefor J, Lich KE, Liparoto SF, Xiao YQ,
JournalJ Immunol Methods
PubMed ID21767540
Phagocytosis plays a pivotal and essential role in host immune defense, both as a focal constituent of the innate immune response and a bridging element linking innate and adaptive immunity. Phagocytosis has been demonstrated to be critical in development, tissue remodeling, wound healing and resolution of inflammation through clearance of ... More
The activation of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells.
AuthorsTakenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Wei J, Sekigawa A, Sato M, Kojima S, Kitani H, Hashimoto M,
JournalJ Immunol
PubMed ID19201858
Recently, autophagy has been associated with the TLR signaling pathway to eliminate intracellular pathogens in the innate immune system. However, it is unknown if other pathways regulate autophagy during the immunologic response. Given the critical role of the purinergic P2X7 receptor (P2X7R) pathway during various immunologic functions (i.e., caspase activation ... More