PMID- 16162269 OWN - NLM STAT- MEDLINE DCOM- 20051110 LR - 20181113 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 116 IP - 2 DP - 2005 Oct TI - Differential effects of CpG-DNA in Toll-like receptor-2/-4/-9 tolerance and cross-tolerance. PG - 203-12 AB - Lipopolysaccharide (LPS) tolerance is a state of refractoriness towards a second stimulation by LPS after a preceding stimulation. LPS is recognized by Toll-like receptor-4 (TLR-4), which belongs to a group of pattern recognition receptors mediating activation of innate immunity by microbial components. To date, it is not known in detail to what extent other TLR-dependent stimuli also induce tolerance and whether preceding and challenging stimuli are interchangeable. We have examined tolerance induction in detail for lipoteichoic acid (LTA), LPS and CpG-DNA, which are recognized by TLR-2, -4 and -9, respectively. In RAW264.7 macrophages, all three stimuli induced tolerance towards a subsequent challenge with the same stimulus used for priming, as well as cross-tolerance towards subsequent challenge with other stimuli signalling via different TLRs. However, whereas LPS/LTA cross-tolerance was also functional in an in vivo model of galactosamine (GalN)-primed liver damage, pretreatment with CpG only protected against GalN/CpG challenge and failed to induce cross-tolerance for LPS and LTA. CpG-DNA pretreatment even enhanced tumour necrosis factor (TNF)-alpha production and liver damage upon subsequent challenge with LPS or LTA. Stimulation with CpG-DNA resulted in a peculiar sensitization for interferon (IFN)-gamma secretion. The data indicate that, in contrast to in vitro macrophage desensitization, the in vivo consequences of repeated TLR stimulation greatly differ amongst different TLR ligands. FAU - Dalpke, Alexander H AU - Dalpke AH AD - Institute of Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany. alexander.dalpke@med.uni-heidelberg.de FAU - Lehner, Martin D AU - Lehner MD FAU - Hartung, Thomas AU - Hartung T FAU - Heeg, Klaus AU - Heeg K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (CPG-oligonucleotide) RN - 0 (DNA-Binding Proteins) RN - 0 (Interleukin-18) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Immunologic) RN - 0 (Teichoic Acids) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Tlr9 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 9) RN - 0 (Toll-Like Receptors) RN - 56411-57-5 (lipoteichoic acid) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cells, Cultured MH - Chemical and Drug Induced Liver Injury/immunology MH - CpG Islands MH - DNA-Binding Proteins/immunology MH - *Immune Tolerance MH - Interferon-gamma/biosynthesis MH - Interleukin-18/biosynthesis/immunology MH - Ligands MH - Lipopolysaccharides/immunology MH - Macrophages, Peritoneal/immunology MH - Membrane Glycoproteins/*immunology MH - Mice MH - Mice, Inbred Strains MH - Oligodeoxyribonucleotides/*immunology MH - Receptors, Cell Surface/*immunology MH - Receptors, Immunologic/immunology MH - Teichoic Acids/immunology MH - Toll-Like Receptor 2 MH - Toll-Like Receptor 4 MH - Toll-Like Receptor 9 MH - Toll-Like Receptors PMC - PMC1817820 EDAT- 2005/09/16 09:00 MHDA- 2005/11/11 09:00 PMCR- 2006/10/01 CRDT- 2005/09/16 09:00 PHST- 2005/09/16 09:00 [pubmed] PHST- 2005/11/11 09:00 [medline] PHST- 2005/09/16 09:00 [entrez] PHST- 2006/10/01 00:00 [pmc-release] AID - IMM2211 [pii] AID - 10.1111/j.1365-2567.2005.02211.x [doi] PST - ppublish SO - Immunology. 2005 Oct;116(2):203-12. doi: 10.1111/j.1365-2567.2005.02211.x.