| Simultaneous blocking of human Toll-like receptors 2 and 4 suppresses myeloid dendritic cell activation induced by Mycobacterium bovis bacillus Calmette-Guérin peptidoglycan. | |
| | |
MedLine Citation:
|
PMID: 12874299 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The Mycobacterium bovis bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) consists of mycolic acids, arabinogalactan, and peptidoglycan (PGN) and activates Toll-like receptor 2 (TLR2) and TLR4. Here we investigated the ability of the essential portion of highly purified BCG CWS to support the TLR agonist function by using the following criteria: myeloid dendritic cell (DC) maturation, i.e., tumor necrosis factor alpha (TNF-alpha) production and CD83/CD86 up-regulation. The purified PGN region was sufficient to activate TLR2 and TLR4 in mouse DCs and macrophages; in TLR2 and TLR4 double-knockout cells the BCG PGN-mediated TNF-alpha production ability was completely impaired. Likewise, stimulation with BCG CWS of HEK293 cells expressing either human TLR2 or TLR4, MD-2, and CD14 resulted in NF-kappa B activation as determined by a reporter assay. Notably, specific blockers of extracellular human TLR2 (an original cocktail of monoclonal antibodies TLR2.45 and TH2.1) and TLR4 (E5531) inhibited BCG CWS-mediated NF-kappa B activation by 80%. Using this human TLR blocking system, we tested whether human myeloid DC maturation was TLR2 and TLR4 dependent. BCG PGN-mediated DC maturation was blocked by 70% by suppression of both TLR2 and TLR4 and by 30 to 40% by suppression of either of these TLRs. Similar but less profound suppression of BCG CWS-mediated DC maturation was observed. Hence, the presence of BCG PGN is a minimal requirement for activation of both TLR2 and TLR4 in human DCs, unlike the presence of PGNs of gram-positive bacteria, which activate only TLR2. Unexpectedly, however, BCG PGN, unlike BCG CWS, barely activated NF-kappa B in HEK293 cells coexpressing TLR2 plus TLR1, TLR2 plus TLR4, TLR2 plus TLR6, or TLR2 plus TLR10, suggesting that PGN receptors other than TLR2 and TLR4 present on human DCs but not on HEK293 cells are involved in TLR signaling for DC activation. |
| | |
Authors:
|
Junji Uehori; Misako Matsumoto; Shoutaro Tsuji; Takashi Akazawa; Osamu Takeuchi; Shizuo Akira; Tsutomu Kawata; Ichiro Azuma; Kumao Toyoshima; Tsukasa Seya |
Related Documents
:
|
18064709 - Effects of inflammatory response on in vivo transgene expression by plasmid dna in mice. 16275389 - Il-17 suppresses tnf-alpha-induced ccl27 production through induction of cox-2 in human... 8409429 - Antioxidant treatment of thymic organ cultures decreases nf-kappa b and tcf1(alpha) tra... 12406389 - Inhibition of lps-induced nitric oxide and tnf-alpha production by alpha-lipoic acid in... 11254529 - Ventilation-induced chemokine and cytokine release is associated with activation of nuc... 12016129 - Il-17 stimulates inflammatory responses via nf-kappab and map kinase pathways in human ... 3020299 - Influence of age on induction of mammary tumors by diethylstilbestrol in c3h/hen mice w... 9521049 - Selective tolerization of th1-like cells after nasal administration of a cholera toxoid... 11068209 - Il-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in a... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Infection and immunity Volume: 71 ISSN: 0019-9567 ISO Abbreviation: Infect. Immun. Publication Date: 2003 Aug |
Date Detail:
|
Created Date: 2003-07-22 Completed Date: 2003-08-26 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
|
Languages: eng Pagination: 4238-49 Citation Subset: IM |
Affiliation:
|
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antibodies, Monoclonal / pharmacology Cell Differentiation / drug effects Cell Wall / chemistry, immunology Dendritic Cells / cytology, drug effects*, immunology* Humans Membrane Glycoproteins / antagonists & inhibitors*, immunology, metabolism Mice Mice, Knockout Mycobacterium bovis / chemistry, immunology* Peptidoglycan / metabolism, pharmacology* Receptors, Cell Surface / antagonists & inhibitors*, immunology, metabolism Toll-Like Receptor 1 Toll-Like Receptor 10 Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors |
| Grant Support | |
ID/Acronym/Agency:
|
AI41667/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Membrane Glycoproteins; 0/Peptidoglycan; 0/Receptors, Cell Surface; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 1; 0/Toll-Like Receptor 10; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Toll-Like Receptors |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Survival, replication, and antibody susceptibility of Ehrlichia chaffeensis outside of host cells.
Next Document: Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylo...