Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) provides an essential component of immunity to tuberculosis by activating infected host macrophages to directly inhibit the replication of Mycobacterium tuberculosis (Mtb). IFN-gamma-inducible nitric oxide synthase 2 (NOS2) is considered a principal effector mechanism, although other pathways may also exist. Here, we identify one member of a newly emerging 47-kilodalton (p47) guanosine triphosphatase family, LRG-47, that acts independently of NOS2 to protect against disease. Mice lacking LRG-47 failed to control Mtb replication, unlike those missing the related p47 guanosine triphosphatases IRG-47 or IGTP. Defective bacterial killing in IFN-gamma-activated LRG-47-/- macrophages was associated with impaired maturation of Mtb-containing phagosomes, vesicles that otherwise recruited LRG-47 in wild-type cells. Thus, LRG-47 may serve as a critical vacuolar trafficking component used to dispose of intracellular pathogens like Mtb.
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PMID:Immune control of tuberculosis by IFN-gamma-inducible LRG-47. 1457 37

Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for the elimination of intracellular Mycobacterium tuberculosis. We also identified a function for a human IRG protein in the control of intracellular pathogens and report that the human Irgm1 ortholog, IRGM, plays a role in autophagy and in the reduction of intracellular bacillary load.
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PMID:Human IRGM induces autophagy to eliminate intracellular mycobacteria. 1688 3

Toll-like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88-dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yet-unknown mechanism that may involve increased phagosome maturation.
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PMID:Engagement of Toll-like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non-oxidative and TNF-independent anti-mycobacterial activity. 1862 55