Regulation of mammalian defensin expression by Toll-like receptor-dependent and independent signalling pathways.
The immune system consists of innate and adaptive immune responses. The innate immune system confers non-specific protection against a large number of pathogens, hence, serving as the first line of defence. The innate immune system utilizes Toll-like receptors (TLRs) to recognize and bind pathogen-associated molecular patterns (PAMPs). Binding of PAMPs leads to TLR activation, which, in turn, initiates MAPK- or NF-kappaB-dependent cascades that culminate in a proinflammatory response. This response involves the secretion of cytokines, chemokines and broad-spectrum antibacterial substances, such as defensins. Increased defensin synthesis is also mediated by the activation of receptors other than TLRs, such as NOD2, IL-17R and PAR-2. This review summarizes the recently characterized signalling pathways leading to increased defensin synthesis as well as the pathway by which defensins activate TLRs on immature dendritic and memory T cells. Thus, not only do defensins eliminate pathogens, but they also recruit the adaptive immune system in instances of infection and/or inflammation.
Froy
Oren
O
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food, and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel. froy@agri.huji.ac.il
D000595:Amino Acid Sequence; D000818:Animals; D023082:Defensins / Q000096:biosynthesis*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
D023082:Defensins; D051193:Toll-Like Receptors