排序方式: 共有128条查询结果,搜索用时 62 毫秒
91.
92.
Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. 总被引:24,自引:0,他引:24
M A Campos I C Almeida O Takeuchi S Akira E P Valente D O Procópio L R Travassos J A Smith D T Golenbock R T Gazzinelli 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(1):416-423
Glycosylphosphatidylinositol (GPI) anchors and glycoinositolphospholipids (GIPLs) from parasitic protozoa have been shown to exert a wide variety of effects on cells of the host innate immune system. However, the receptor(s) that are triggered by these protozoan glycolipids has not been identified. Here we present evidence that Trypanosoma cruzi-derived GPI anchors and GIPLs trigger CD25 expression on Chinese hamster ovary-K1 cells transfected with CD14 and Toll-like receptor-2 (TLR-2), but not wild-type (TLR-2-deficient) Chinese hamster ovary cells. The protozoan-derived GPI anchors and GIPLs containing alkylacylglycerol and saturated fatty acid chains or ceramide were found to be active in a concentration range of 100 nM to 1 microM. More importantly, the GPI anchors purified from T. cruzi trypomastigotes, which contain a longer glycan core and unsaturated fatty acids in the sn-2 position of the alkylacylglycerolipid component, triggered TLR-2 at subnanomolar concentrations. We performed experiments with macrophages from TLR-2 knockout and TLR-4 knockout mice, and found that TLR-2 expression appears to be essential for induction of IL-12, TNF-alpha, and NO by GPI anchors derived from T. cruzi trypomastigotes. Thus, highly purified GPI anchors from T. cruzi parasites are potent activators of TLR-2 from both mouse and human origin. The activation of TLR-2 may initiate host innate defense mechanisms and inflammatory response during protozoan infection, and may provide new strategies for immune intervention during protozoan infections. 相似文献
93.
Novel engagement of CD14 and multiple toll-like receptors by group B streptococci. 总被引:11,自引:0,他引:11
P Henneke O Takeuchi J A van Strijp H K Guttormsen J A Smith A B Schromm T A Espevik S Akira V Nizet D L Kasper D T Golenbock 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(12):7069-7076
Group B streptococcus (GBS) imposes a major health threat to newborn infants. Little is known about the molecular basis of GBS-induced sepsis. Both heat-inactivated whole GBS bacteria and a heat-labile soluble factor released by GBS during growth (GBS-F) induce nuclear translocation of NF-kappaB, the secretion of TNF-alpha, and the formation of NO in mouse macrophages. Macrophages from mice with a targeted disruption of MyD88 failed to secrete TNF-alpha in response to both heat-inactivated whole bacteria and GBS-F, suggesting that Toll-like receptors (TLRs) are involved in different aspects of GBS recognition. Immune cell activation by whole bacteria differed profoundly from that by secreted GBS-F. Whole GBS activated macrophages independently of TLR2 and TLR6, whereas a response to the secreted GBS-F was not observed in macrophages from TLR2-deficient animals. In addition to TLR2, TLR6 and CD14 expression were essential for GBS-F responses, whereas TLR1 and TLR4 or MD-2 did not appear to be involved. Heat lability distinguished GBS-F from peptidoglycan and lipoproteins. GBS mutants deficient in capsular polysaccharide or beta-hemolysin had GBS-F activity comparable to that of wild-type streptococci. We suggest that CD14 and TLR2 and TLR6 function as coreceptors for secreted microbial products derived from GBS and that cell wall components of GBS are recognized by TLRs distinct from TLR1, 2, 4, or 6. 相似文献
94.
Hannah Scheiblich Anna Schlütter Douglas T. Golenbock Eicke Latz Pilar Martinez‐Martinez Michael T. Heneka 《Journal of neurochemistry》2017,143(5):534-550
95.
Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. 总被引:23,自引:0,他引:23
T K Means S Wang E Lien A Yoshimura D T Golenbock M J Fenton 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(7):3920-3927
Recent studies have implicated a family of mammalian Toll-like receptors (TLR) in the activation of macrophages by Gram-negative and Gram-positive bacterial products. We have previously shown that different TLR proteins mediate cellular activation by the distinct CD14 ligands Gram-negative bacterial LPS and mycobacterial glycolipid lipoarabinomannan (LAM). Here we show that viable Mycobacterium tuberculosis bacilli activated both Chinese hamster ovary cells and murine macrophages that overexpressed either TLR2 or TLR4. This contrasted with Gram-positive bacteria and Mycobacterium avium, which activated cells via TLR2 but not TLR4. Both virulent and attenuated strains of M. tuberculosis could activate the cells in a TLR-dependent manner. Neither membrane-bound nor soluble CD14 was required for bacilli to activate cells in a TLR-dependent manner. We also assessed whether LAM was the mycobacterial cell wall component responsible for TLR-dependent cellular activation by M. tuberculosis. We found that TLR2, but not TLR4, could confer responsiveness to LAM isolated from rapidly growing mycobacteria. In contrast, LAM isolated from M. tuberculosis or Mycobacterium bovis bacillus Calmette-Guérin failed to induce TLR-dependent activation. Lastly, both soluble and cell wall-associated mycobacterial factors were capable of mediating activation via distinct TLR proteins. A soluble heat-stable and protease-resistant factor was found to mediate TLR2-dependent activation, whereas a heat-sensitive cell-associated mycobacterial factor mediated TLR4-dependent activation. Together, our data demonstrate that Toll-like receptors can mediate cellular activation by M. tuberculosis via CD14-independent ligands that are distinct from the mycobacterial cell wall glycolipid LAM. 相似文献
96.
Patricia Langjahr David Díaz-Jiménez Marjorie De la Fuente Estefhany Rubio Douglas Golenbock Francisca C. Bronfman Rodrigo Quera María-Julieta González Marcela A. Hermoso 《PloS one》2014,9(12)
Toll-like receptor (TLR) 2, a type I membrane receptor that plays a key role in innate immunity, recognizes conserved molecules in pathogens, and triggering an inflammatory response. It has been associated with inflammatory and autoimmune diseases. Soluble TLR2 (sTLR2) variants have been identified in human body fluids, and the TLR2 ectodomain can negatively regulate TLR2 activation by behaving as a decoy receptor. sTLR2 generation does not involve alternative splicing mechanisms, indicating that this process might involve a post-translational modification of the full-length receptor; however, the specific mechanism has not been studied. Using CD14+ peripheral human monocytes and the THP-1 monocytic leukemia-derived cell line, we confirm that sTLR2 generation increases upon treatment with pro-inflammatory agents and requires a post-translational mechanism. We also find that the constitutive and ligand-induced release of sTLR2 is sensitive to pharmacological metalloproteinase activator and inhibitors leading us to conclude that metalloproteinase TLR2 shedding contributes to soluble receptor production. By expressing human TLR2 in ADAM10- or ADAM17-deficient MEF cells, we find both enzymes to be implicated in TLR2 ectodomain shedding. Moreover, using a deletion mutant of the TLR2 juxtamembrane region, we demonstrate that this domain is required for sTLR2 generation. Functional analysis suggests that sTLR2 generated by metalloproteinase activation inhibitsTLR2-induced cytokine production by this monocytic leukemia-derived cell line. The identification of the mechanisms involved in regulating the availability of soluble TLR2 ectodomain and cell surface receptors may contribute further research on TLR2-mediated processes in innate immunity and inflammatory disorders. 相似文献
97.
Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition 总被引:5,自引:0,他引:5
Wang JP Liu P Latz E Golenbock DT Finberg RW Libraty DH 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(10):7114-7121
TLR7 senses RNA in endosomal compartments. TLR7 expression and signaling have been demonstrated in plasmacytoid and myeloid dendritic cells, B cells, and T cells. The regulation of TLR7 signaling can play a crucial role in shaping the immune response to RNA viruses with different cellular tropisms, and in developing adjuvants capable of promoting balanced humoral and cell-mediated immunity. We used unique characteristics of two ssRNA viruses, dengue virus and influenza virus, to delineate factors that regulate viral RNA-human TLR7 signaling beyond recognition in endosomal compartments. Our data show that TLR7 recognition of enveloped RNA virus genomes is linked to virus fusion or uncoating from the endosome. The signaling threshold required to activate TLR7-type I IFN production is greater than that required to activate TLR7-NF-kappaB-IL-8 production. The higher order structure of viral RNA appears to be an important determinant of TLR7-signaling potency. A greater understanding of viral RNA-TLR7 activity relationships will promote rational approaches to interventional and vaccine strategies for important human viral pathogens. 相似文献
98.
Facundo Davaro Sorcha D. Forde Mark Garfield Zhaozhao Jiang Kristen Halmen Nelsy Depaula Tamburro Evelyn Kurt-Jones Katherine A. Fitzgerald Douglas T. Golenbock Donghai Wang 《The Journal of biological chemistry》2014,289(23):16214-16222
Multiple clinical trials have shown that the 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known as statins have anti-inflammatory effects. However, the underlying molecular mechanism remains unclear. The proinflammatory cytokine interleukin-1β (IL-1β) is synthesized as a non-active precursor. The 31-kDa pro-IL-1β is processed into the 17-kDa active form by caspase-1-activating inflammasomes. Here, we report a novel signaling pathway induced by statins, which leads to processing of pro-IL-1β into an intermediate 28-kDa form. This statin-induced IL-1β processing is independent of caspase-1- activating inflammasomes. The 28-kDa form of IL-1β cannot activate interleukin-1 receptor-1 (IL1R1) to signal inflammatory responses. Instead, it interferes with mature IL-1β signaling through IL-1R1 and therefore may dampen inflammatory responses initiated by mature IL-1β. These results may provide new clues to explain the anti-inflammatory effects of statins. 相似文献
99.
100.
Phylogenetic evidence for role-reversals of gender-associated mitochondrial DNA in Mytilus (Bivalvia: Mytilidae) 总被引:1,自引:0,他引:1
Hoeh WR; Stewart DT; Saavedra C; Sutherland BW; Zouros E 《Molecular biology and evolution》1997,14(9):959-967
Distinct gender-associated mitochondrial DNA (mtDNA) lineages (i.e.,
lineages which are transmitted either through males or through females)
have been demonstrated in two families of bivalves, the Mytilidae (marine
mussels) and the Unionidae (freshwater mussels), which have been separated
for more than 400 Myr. The mode of transmission of these M (for
male-transmitted) and F (for female-transmitted) molecules has been
referred to as doubly uniparental inheritance (DUI), in contrast to
standard maternal inheritance (SMI), which is the norm in animals. A
previous study suggested that at least three origins of DUI are required to
explain the phylogenetic pattern of M and F lineages in freshwater and
marine mussels. Here we present phylogenetic evidence based on partial
sequences of the cytochrome c oxidase subunit I gene and the 16S RNA gene
that indicates the DUI is a dynamic phenomenon. Specifically, we
demonstrate that F lineages in three species of Mytilus mussels, M. edulis,
M. trossulus, and M. californianus, have spawned separate lineages which
are now associated only with males. This process is referred to as
"masculinization" of F mtDNA. By extension, we propose that DUI may be a
primitive bivalve character and that periodic masculinization events
combined with extinction of previously existing M types effectively reset
the time of divergence between conspecific gender-associated mtDNA
lineages.
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