| Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production. | |
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MedLine Citation:
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PMID: 21088052 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Lipopolysaccharide is a major constituent of the outer membrane of Gram-negative bacteria and important in the induction of pro-inflammatory responses. Recently, novel LPS species derived from Neisseria meningitidis H44/76 by insertional inactivation of the lpxL1 and lpxL2 genes have been created with a lipid A portion consisting of five (penta-acylated lpxL1) or four (tetra-acylated lpxL2) fatty acids connected to the glucosamine backbone instead of six fatty acids in the wild-type LPS. We show that these mutant LPS-types are poor inducers of cytokines (tumor-necrosis factor-α, IL-1β, IL-10, IL-RA) in human mononuclear cells. Both penta- and tetra-acylated meningococcal LPSs were able to inhibit cytokine production by wild-type Escherichia coli or meningococcal LPS. Binding of FITC-labelled E. coli LPS TLR4 transfected Chinese hamster ovary (CHO) cells was inhibited by both mutant LPS-types. Experiments with CHO fibroblasts transfected with human CD14 and TLR4 showed that the antagonizing effect was dependent on the expression of human TLR4. In contrast to the situation in humans, lpxL1 LPS has agonistic activity for cytokine production in peritoneal macrophages of DBA mice, and exacerbated arthritis in murine collagen induced arthritis model. N. meningitidis lipid A mutant LPSs lpxL1 and lpxL2 function as LPS antagonists in humans by inhibiting TLR4-dependent cytokine production but have agonistic activity in mice. |
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Authors:
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Tom Sprong; Peter van der Ley; Shahla Abdollahi-Roodsaz; Leo Joosten; Jos van der Meer; Mihai Netea; Marcel van Deuren |
Publication Detail:
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Type: Journal Article Date: 2010-11-18 |
Journal Detail:
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Title: Innate immunity Volume: 17 ISSN: 1753-4267 ISO Abbreviation: Innate Immun Publication Date: 2011 |
Date Detail:
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Created Date: 2011-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101469670 Medline TA: Innate Immun Country: United States |
Other Details:
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Languages: eng Pagination: 517-25 Citation Subset: IM |
Affiliation:
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1Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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