دورية أكاديمية

Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production

التفاصيل البيبلوغرافية
العنوان: Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production
المؤلفون: Sprong, Tom, Ley, Peter van der, Abdollahi-Roodsaz, Shahla, Joosten, Leo, Meer, Jos van der, Netea, Mihai, Deuren, Marcel van
المصدر: Innate Immunity ; volume 17, issue 6, page 517-525 ; ISSN 1753-4259 1753-4267
بيانات النشر: SAGE Publications
سنة النشر: 2010
مصطلحات موضوعية: Infectious Diseases, Cell Biology, Molecular Biology, Immunology, Microbiology
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1177/1753425910383999
الإتاحة: https://doi.org/10.1177/1753425910383999Test
حقوق: http://journals.sagepub.com/page/policies/text-and-data-mining-licenseTest
رقم الانضمام: edsbas.1E444DA6
قاعدة البيانات: BASE