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Your search keyword '"Toll-Like Receptor 6 deficiency"' showing total 2 results
Start Over Descriptor "Toll-Like Receptor 6 deficiency" Topic toll-like receptor 2
2 results on '"Toll-Like Receptor 6 deficiency"'

1. TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia.

Author

Biswas S, Zimman A, Gao D, Byzova TV, and Podrez EA

Subjects
Animals, Apolipoproteins E deficiency, Apolipoproteins E genetics, Blood Platelets immunology, CD36 Antigens deficiency, CD36 Antigens genetics, Disease Models, Animal, Female, Genetic Predisposition to Disease, HEK293 Cells, Humans, Hyperlipidemias blood, Hyperlipidemias genetics, Hyperlipidemias immunology, Immunity, Innate, Male, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88 deficiency, Myeloid Differentiation Factor 88 genetics, Oxidation-Reduction, Phenotype, Phospholipids blood, Signal Transduction, Thrombosis blood, Thrombosis genetics, Thrombosis immunology, Toll-Like Receptor 2 deficiency, Toll-Like Receptor 2 genetics, Toll-Like Receptor 6 deficiency, Toll-Like Receptor 6 genetics, Toll-Like Receptor 6 metabolism, Transfection, Blood Platelets metabolism, Hyperlipidemias metabolism, Platelet Activation, Thrombosis metabolism, Toll-Like Receptor 2 metabolism
Abstract

Rationale: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood., Objective: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to the accumulation in the circulation of a specific group of oxidized phospholipids (oxPC CD36 ) that are ligands for the platelet pattern recognition receptor CD36. In the current article, we tested whether the platelet innate immune system contributes to responses to oxPC CD36 and accelerated thrombosis observed in hyperlipidemia., Methods and Results: Using in vitro approaches, as well as platelets from mice with genetic deletion of MyD88 (myeloid differentiation factor 88) or TLRs (Toll-like receptors), we demonstrate that TLR2 and TLR6 are required for the activation of human and murine platelets by oxPC CD36 . oxPC CD36 induce formation of CD36/TLR2/TLR6 complex in platelets and activate downstream signaling via TIRAP (Toll-interleukin 1 receptor domain containing adaptor protein)-MyD88-IRAK (interleukin-1 receptor-associated kinase)1/4-TRAF6 (TNF receptor-associated factor 6), leading to integrin activation via the SFK (Src family kinase)-Syk (spleen tyrosine kinase)-PLCγ2 (phospholipase Cγ2) pathway. Intravital thrombosis studies using ApoE -/- mice with genetic deficiency of TLR2 or TLR6 have demonstrated that oxPC CD36 contribute to accelerated thrombosis specifically in the setting of hyperlipidemia., Conclusions: Our studies reveal that TLR2 plays a key role in platelet hyperreactivity and the prothrombotic state in the setting of hyperlipidemia by sensing a wide range of endogenous lipid peroxidation ligands and activating innate immune signaling cascade in platelets., (© 2017 American Heart Association, Inc.)

Published
2017
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2. Role for MyD88, TLR2 and TLR9 but not TLR1, TLR4 or TLR6 in experimental autoimmune encephalomyelitis.

Author

Miranda-Hernandez S, Gerlach N, Fletcher JM, Biros E, Mack M, Körner H, and Baxter AG

Subjects
Animals, Cell Movement genetics, Cell Movement immunology, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental genetics, Female, Gene Silencing, Genetic Predisposition to Disease, Glycoproteins administration & dosage, Glycoproteins toxicity, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myelin-Oligodendrocyte Glycoprotein, Myeloid Differentiation Factor 88 deficiency, Nerve Tissue Proteins administration & dosage, Nerve Tissue Proteins toxicity, Peptide Fragments administration & dosage, Peptide Fragments toxicity, Severity of Illness Index, Signal Transduction genetics, Signal Transduction immunology, Toll-Like Receptor 2 deficiency, Toll-Like Receptor 9 deficiency, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental prevention & control, Myeloid Differentiation Factor 88 physiology, Toll-Like Receptor 1 deficiency, Toll-Like Receptor 2 physiology, Toll-Like Receptor 4 deficiency, Toll-Like Receptor 6 deficiency, Toll-Like Receptor 9 physiology
Abstract

The potential roles of TLRs in the cause and pathogenesis of autoimmune CNS inflammation remain contentious. In this study, we examined the effects of targeted deletions of TLR1, TLR2, TLR4, TLR6, TLR9, and MyD88 on the induction of myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide/CFA/pertussis toxin-induced autoimmune encephalomyelitis. Although C57BL/6.Tlr1(-/-), C57BL/6.Tlr4(-/-) and C57BL/6.Tlr6(-/-) mice showed normal susceptibility to disease, signs were alleviated in female C57BL/6.Tlr2(-/-) and C57BL/6.Tlr9(-/-) mice and C57BL/6.Tlr2/9(-/-) mice of both sexes. C57BL/6.Myd88(-/-) mice were completely protected. Lower clinical scores were associated with reduced leukocyte infiltrates. These results were confirmed by passive adoptive transfer of disease into female C57BL/6.Tlr2(-/-) and C57BL/6.Tlr9(-/-) mice, where protection in the absence of TLR2 was associated with fewer infiltrating CD4(+) cells in the CNS, reduced prevalence of detectable circulating IL-6, and increased proportions of central (CD62L(+)) CD4(+)CD25(+)Foxp3(+) regulatory T cells. These results provide a potential molecular mechanism for the observed effects of TLR signaling on the severity of autoimmune CNS inflammation.

Published
2011
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