Udział receptora TLR-5 w mechanizmach odpowiedzi immunologicznej: fizjologia i patologia
The innate immune system is equipped with receptors that recognize microbe specific molecular structures (also called pathogen-associated molecular patterns or PAMPs). Responses to extracellular PAMPs are mediated through transmembrane receptors such as the Toll-like receptors (TLRs). Out of 13 known mammalian TLRs, a special role may be attributed to TLR-5 since it recognizes flagellin, a major structural protein of bacterial flagella. Similarly to other TLRs, ligation of TLR-5 induces the expression of proinflammatory cytokines, chemokines, adhesion molecules and other antimicrobial defense molecules by the activation of transcription factor NFKB. Apart from activating innate immune responses flagellin is also an efficient antigen that stimulates both B and T lymphocytes. The adjuvant properties of flagellin have been exploited for the preparation of experimental vaccines. Recent observations indicate an important role of the flagellin-TLR-5 interactions in the pathomechanisms of Crohn’s disease and pneumonia caused by the Pseudomonas aerugonosa. Polymorphisms in the TLR-5 gene may be associated with protection from Crohn’s disease and systemic lupus erythematosus (SLE). Further studies on recently created genetic models of TLR-5 and other TLRs knockout mice will expand our knowledge about flagellin and TLR-5 function in health and disease.