Endotoxin tolerance: new mechanisms, molecules and clinical significance.
Prior exposure of innate immune cells like monocytes/macrophages to minute amounts of endotoxin cause them to become refractory to subsequent endotoxin challenge, a phenomenon called "endotoxin tolerance". Clinically, this state is associated with monocytes/macrophages in sepsis patients where they contribute to "immunosuppression" and mortality. The molecular mechanisms underlying endotoxin tolerance remain elusive. The recent appreciation of inflammation as a self-regulating process, the relative contribution of MyD88 versus TRIF signaling pathways in inducing activation or tolerance, plasticity of NF-kappaB function and the role of chromatin modification and microRNAs in LPS-induced gene reprogramming urges a re-evaluation of endotoxin tolerance. This review integrates these new findings into an up-to-date account of endotoxin tolerance, its molecular basis and clinical implications in different pathologies.
Singapore Immunology Network, Biomedical Sciences Institutes, Agency for Science, Technology and Research, #04-01 Immunos, 8A Biomedical Drive, 138648 Singapore. subhra_biswas@immunol.a-star.edu.sg
Subhra K
SK
Biswas
Eduardo
E
Lopez-Collazo
D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000378:metabolism; D004731:Endotoxins / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism; D009000:Monocytes / Q000502:physiology; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
D002843:Chromatin; D004731:Endotoxins; D035683:MicroRNAs; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors