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Innate Immunity

Innate immunity is the first line of defense against infection. The innate immune system is composed of germ-line encoded receptors that collectively serve as a sensor to monitor extracellular and intracellular compartments for signs of infection or tissue injury. Since the discovery linking Toll in the fly to anti-fungal defense, seminal discoveries have identified families of mammalian Toll-like receptors (TLRs), Nod-like receptors, Rig-I like receptors, C-type lectins, Aim2-like receptors and other DNA sensors and highlighted their ability to recognize microbial products.

Activation of innate immune sensing receptors leads to the transcription of hundreds of genes involved in antimicrobial defense, phagocytosis, cell migration, metabolic reprogramming, tissue repair and regulation of adaptive immunity. These responses curb pathogen growth and spread and also mobilize the T-cells and B-cells of the adaptive immune system. The ability of the innate immune system to mobilize, instruct and regulate adaptive immunity is well established.

For some of these receptors, the downstream response involves activation of the proteolytic enzyme caspase-1 leading to the maturation of the IL-1 family of cytokines.