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Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. - eScholarship
Jessica A. Hamerman,Nadia K. Tchao,Clifford A. Lowell,Lewis L. Lanier +3 more
- Vol. 6, Iss: 6, pp 579-586
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TLDR
This article examined the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs) and found that one or more DAP-pairing receptors negatively regulate signaling through TLRs.Abstract:
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.read more
Citations
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Syk Facilitates Influenza A Virus Replication by Restraining Innate Immunity at the Late Stage of Viral Infection
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References
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On Toll-like receptors and the innate immune response in sepsis caused by Burkholderia pseudomallei (melioidosis)
TL;DR: Melioidosis is caused by the aerobic Gram-negative soil-dwelling bacillus Burkholderia pseudomallei and is an important cause of severe sepsis in Southeast Asia and Northern Australia and is a potential bioterror agent.
Posted ContentDOI
Suppression of homeostatic gene expression and increased expression of metabolism-related genes are early features of glaucoma in optic nerve head microglia
TL;DR: Microglia become metabolically primed early in glaucoma pathogenesis with suppression of homeostatic regulation including phagocytosis, inflammatory, and sensome pathways and radiation therapy potently abolishes these microglia metabolic transcriptomic changes.
Journal ArticleDOI
Роль триггерного рецептора, экспрессируемого на миелоидных клетках, в активации врожденного иммунитета
TL;DR: The innate immune system plays a key role in triggering a systemic inflammatory response (SIR), by regulating the effector mechanisms of innate immunity, and the simultaneous activation of Toll-like receptors and TREM-1 increases the production of cytokines manifold.