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dc.contributor.authorJain, Vishal
dc.contributor.authorHalle, Annett
dc.contributor.authorHalmen, Kristen A.
dc.contributor.authorLien, Egil
dc.contributor.authorCharrel-Dennis, Marie
dc.contributor.authorRam, Sanjay
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorVisintin, Alberto
dc.date2022-08-11T08:09:37.000
dc.date.accessioned2022-08-23T16:37:57Z
dc.date.available2022-08-23T16:37:57Z
dc.date.issued2008-01-22
dc.date.submitted2009-10-29
dc.identifier.citation<p>Blood. 2008 May 1;111(9):4637-45. Epub 2008 Jan 18. <a href="http://dx.doi.org/10.1182/blood-2007-11-126862">Link to article on publisher's site</a></p>
dc.identifier.issn1528-0020 (Electronic)
dc.identifier.doi10.1182/blood-2007-11-126862
dc.identifier.pmid18203953
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39140
dc.description.abstractBoth Toll-like receptor 4 (TLR4)- and MD-2-deficient mice succumb to otherwise nonfatal gram-negative bacteria inocula, demonstrating the pivotal role played by these proteins in antibacterial defense in mammals. MD-2 is a soluble endogenous ligand for TLR4 and a receptor for lipopolysaccharide (LPS). LPS-bound MD-2 transmits an activating signal onto TLR4. In this report, we show that both recombinant and endogenous soluble MD-2 bind tightly to the surface of live gram-negative bacteria. As a consequence, MD-2 enhances cellular activation, bacterial internalization, and intracellular killing, all in a TLR4-dependent manner. The enhanced internalization of MD-2-coated bacteria was not observed in macrophages expressing Lps(d), a signaling-incompetent mutant form of TLR4, suggesting that the enhanced phagocytosis observed is dependent on signal transduction. The data confirm the notion that soluble MD-2 is a genuine opsonin that enhances proinflammatory opsonophagocytosis by bridging live gram-negative bacteria to the LPS transducing complex. The presented results extend our understanding of the role of the TLR4/MD-2 signaling axis in bacterial recognition by phagocytes.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18203953&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2343597/
dc.subjectAnimals
dc.subjectGram-Negative Bacteria
dc.subjectLymphocyte Antigen 96
dc.subjectMice
dc.subjectOpsonin Proteins
dc.subject*Phagocytosis
dc.subjectSignal Transduction
dc.subjectToll-Like Receptor 4
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titlePhagocytosis and intracellular killing of MD-2 opsonized gram-negative bacteria depend on TLR4 signaling
dc.typeJournal Article
dc.source.journaltitleBlood
dc.source.volume111
dc.source.issue9
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1954
dc.identifier.contextkey1050690
html.description.abstract<p>Both Toll-like receptor 4 (TLR4)- and MD-2-deficient mice succumb to otherwise nonfatal gram-negative bacteria inocula, demonstrating the pivotal role played by these proteins in antibacterial defense in mammals. MD-2 is a soluble endogenous ligand for TLR4 and a receptor for lipopolysaccharide (LPS). LPS-bound MD-2 transmits an activating signal onto TLR4. In this report, we show that both recombinant and endogenous soluble MD-2 bind tightly to the surface of live gram-negative bacteria. As a consequence, MD-2 enhances cellular activation, bacterial internalization, and intracellular killing, all in a TLR4-dependent manner. The enhanced internalization of MD-2-coated bacteria was not observed in macrophages expressing Lps(d), a signaling-incompetent mutant form of TLR4, suggesting that the enhanced phagocytosis observed is dependent on signal transduction. The data confirm the notion that soluble MD-2 is a genuine opsonin that enhances proinflammatory opsonophagocytosis by bridging live gram-negative bacteria to the LPS transducing complex. The presented results extend our understanding of the role of the TLR4/MD-2 signaling axis in bacterial recognition by phagocytes.</p>
dc.identifier.submissionpathoapubs/1954
dc.contributor.departmentDivision of Infectious Diseases and Immunology
dc.source.pages4637-45


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