eISSN: 1643-3750


Get your full text copy in PDF

Expression and involvement of Toll-like receptors (TLR)2, TLR4, and CD14 in monocyte TNF-alfa production induced by lipopolysaccharides from Neisseria meningitidis

Mohammad Reza Mirlashari, Torstein Lyberg

Med Sci Monit 2003; 9(8): BR316-324

ID: 13093

Background:The present study was undertaken to examine the ability of lipopolysaccharide-containing outer membrane vesicles (OMV-LPS) and purified LPS (P-LPS) from the same meningococcal strain to induce the expression of Toll-like receptors (TLR2 and TLR4) and TNF-alfa production in leukocytes, and further to study the involvement of TLRs, and CD14 in monocyte TNF- alfa production in an ex vivo human whole blood system.Material/Methods:OMV-LPS or P-LPS were added to human whole blood and expression of TLR2/4 and production of TNF- alfa in leukocytes were measured by flow cytometry. To study involvement of TLRs and CD14 in monocyte cytokine production we used monoclonal antibodies against TLR2/4 and CD14.Results:OMV-LPS and P-LPS induced surface expression (maximal at 120 min) of TLR2 and TLR4 on granulocytes and monocytes. LPS incorporated in OMV was less potent (weight basis) than P-LPS in inducing monocyte TNF- alfa production. When inducing monocyte TNF-alfa by OMV-LPS, antibodies directed against TLR2 and TLR4 caused 45 and 78% inhibition, respectively. When inducing TNF- alfa by P-LPS, antibodies against TLR2 had no effect, whereas anti-TLR4 antibodies caused 63% inhibition. Antibodies against CD14 inhibited nearly completely the monocyte TNF- alfa response induced by meningococcal LPS irrespective of whether LPS was presented in purified form or incorporated in membrane vesicles.Conclusions:OMV-LPS and P-LPS from the same meningococcal strain induced expression of TLR2/4 on monocytes and granulocytes. Surface receptors TLR2/4 and CD14 are essential for in vitro cellular activation induced by OMV-LPS and P-LPS, but the functional significance of these receptors during meningococcal infections remains elusive.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree