Stitaya SirisinhaMahidol University2018-05-032018-05-032011-03-01Asian Pacific Journal of Allergy and Immunology. Vol.29, No.1 (2011), 1-14222886940125877X2-s2.0-79958276436https://repository.li.mahidol.ac.th/handle/123456789/12069Innate and adaptive immune systemsconsist of cells and molecules that worktogether in concert to fight against microbialinfection and maintain homeostasis. Hostsencounter microbes/exogenous pathogenassociatedmolecular patterns (PAMPs) andendogenous damage-associated molecularpatterns (DAMPs) all the time and they musthave proper mechanisms to counteract thedanger such that appropriate responses (e.g.,degree of inflammation and types of mediatorsinduced) can be mounted in differentscenarios. Increasing numbers of endogenousdanger signals of host origin are beingidentified including, for example, uric acid andcholesterol crystals, high mobility group box1(HMGB1) protein, oxidized LDL, vesicans,heat shock proteins (HSPs) and self DNA.Many of these endogenous ligands have beenshown to be associated with inflammationrelateddiseases like atherosclerosis, gout andtype 2 diabetes. Several DAMPs appear to havethe ability to interact with more than onereceptor. We are now beginning to understandhow the immune system can distinguishinfection from endogenous ligands elaboratedfollowing cellular insults and tissue damage.Appropriate responses to maintain thehomeostatic state in health and disease dependlargely on the recognition and response tothese stimuli by germline encoded patternrecognitionreceptors (PRRs) present on bothimmune and non-immune cells. Thesereceptors are, for example, Toll-like receptors(TLRs), C-type lectin receptors (CLRs) andcytosolic receptors (e.g., RLRs, NLRs and someintracellular DNA sensors). Atypical PRR"danger" receptors, like the receptor foradvanced glycation end products (RAGE) andtheir ligands have been identified. A properresponse to maintain homeostasis relies onspecific negative regulators and regulatorypathways to dampen its response to tissueinjury while maintaining the capacity toeliminate infection and induce proper tissuerepair. Moreover, some PRRs (e.g.,TLR2,TLR4 and NLRP3) and atypical PRRscan recognize both PAMPs and DAMPs, eitheras single entities or after forming complexes(e.g., immune complexes, or DNA- HMGB1and DNA-LL37 complexes), so there must be amechanism to selectively depress or alleviatethe inflammatory response to DAMPs, whileleaving that of PAMPs intact. Excessiveinflammatory responses can induceconsiderable tissue damage and can be highlydetrimental to the host. For example, CD24reacting with HMGB1 and HSPs has beenimplicated to function as negative regulator forRAGE. In this review, I will briefly overviewthe information on various host and microbialcomponents and bring together theinformation to synthesize a model to explainhow homeostasis can be maintained in states ofhealth and disease. Understanding themolecular mechanisms by which the immunesystem functions under different scenarios willprovide us with ways and means to designappropriate approaches, for example, toprevent or treat autoimmune andinflammatory diseases or the ability to designnew drugs or formulate safe chemicals forvaccine adjuvants.Mahidol UniversityImmunology and MicrobiologyMedicineReviewSCOPUS