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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
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Microglial TYROBP/DAP12 in Alzheimer’s disease: Transduction of physiological and pathological signals across TREM2
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Dissertation
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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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TL;DR: Surprisingly, a time course study showed that Syk suppressed innate immunity during late phases of IAV infection and thereby promoted IAV replication, providing new insights into complicated mechanisms underlying interaction between virus and host immune system.
References
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Journal ArticleDOI
A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis.
Sébastien Gibot,Marie-Nathalie Kolopp-Sarda,Marie C. Béné,Pierre-Edouard Bollaert,Alain Lozniewski,Françoise Mory,Bruno Levy,Gilbert C. Faure +7 more
TL;DR: Both in vitro and in vivo, a synthetic peptide mimicking a short highly conserved domain of sTREM-1 appeared to attenuate cytokine production by human monocytes and protect septic animals from hyper-responsiveness and death.
Journal ArticleDOI
Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors.
Kevin M. Dennehy,Gerben Ferwerda,Inês Faro-Trindade,Elwira Pyz,Janet A. Willment,Philip R. Taylor,Philip R. Taylor,Ann M. Kerrigan,S. Vicky Tsoni,Siamon Gordon,Friederike Meyer-Wentrup,Gosse J. Adema,Bart Jan Kullberg,Edina Schweighoffer,Victor L. J. Tybulewicz,Héctor M. Mora-Montes,Neil A. R. Gow,David L. Williams,Mihai G. Netea,Gordon D. Brown +19 more
TL;DR: These findings establish the first example of Syk‐ and MyD88‐coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents.
Journal ArticleDOI
Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice
Tomonori Kaifu,Jin Nakahara,Masanori Inui,Kenichi Mishima,Toshihiko Momiyama,Mitsuji Kaji,Akiko Sugahara,Hisami Koito,Azusa Ujike-Asai,Akira Nakamura,Kiyoshi Kanazawa,Kyoko Tan-Takeuchi,Katsunori Iwasaki,Wayne M. Yokoyama,Akira Kudo,Michihiro Fujiwara,Hiroaki Asou,Toshiyuki Takai +17 more
TL;DR: The results provide a molecular basis for a unique combination of skeletal and psychotic characteristics of Nasu-Hakola disease as well as for schizophrenia and presenile dementia.
Journal ArticleDOI
When Signaling Pathways Collide: Positive and Negative Regulation of Toll-like Receptor Signal Transduction
TL;DR: These recent findings emphasize the importance of considering TLR signaling in the context of other signaling pathways, as is likely to occur in vivo during infection and inflammation.
Journal ArticleDOI
A Role for Triggering Receptor Expressed on Myeloid Cells-1 in Host Defense During the Early-Induced and Adaptive Phases of the Immune Response
Joshua R. Bleharski,Viviane Kiessler,Cecilia Buonsanti,Peter A. Sieling,Steffen Stenger,Marco Colonna,Robert L. Modlin +6 more
TL;DR: Primary monocytes differentiated into immature dendritic cells following activation through TREM-1, evidenced by higher expression of CD1a, CD86, and MHC class II molecules and an improved ability to elicit T cell proliferation and production of IFN-γ.