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The expanding role of innate immune receptors

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Innate immune responses constitute the earliest barrier to infectious agents. Evolutionarily, innate immune responses are ancient and constitute the only immunity against pathogens in invertebrates. Adaptive immune responses are induced in vertebrates when innate immunity fails to clear an invading pathogen. ...

Innate immune responses constitute the earliest barrier to infectious agents. Evolutionarily, innate immune responses are ancient and constitute the only immunity against pathogens in invertebrates. Adaptive immune responses are induced in vertebrates when innate immunity fails to clear an invading pathogen. Innate immunity can be viewed as a way to delay an infection until adaptive immunity is induced, which could takes several days depending on the nature of the invading pathogen.

A healthy individual constantly encounters microorganisms throughout his life. However, few encounters lead to an infection. Most of the pathogenic microorganisms are detected and eliminated immediately by innate immune cells, owing to their non-specific and rapid mode of action. Recognition of infectious agents by innate immune cells is mediated with the help of limited genome-encoded receptors that recognize conserved pathogen associated molecular patterns (PAMP). These innate receptors are thus termed pattern recognition receptors (PRR). While some of the innate receptors, such as macrophage mannose receptors (MMR) and macrophage scavenger receptors (MSR) are mainly for recognition and uptake of pathogens, others such as toll-like receptors (TLR), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs) participate in elaborate signaling pathways in multiple innate immune cells leading to cellular activation. The complement system constitutes a panel of soluble molecules that can directly bind to specific complement receptors and recognize conserved pattern on pathogens and altered self. Various innate immune receptors are involved in regulation of innate immune responses. These receptors include various activating and inhibitory receptors on NK cells and the triggering receptor expressed on myeloid cells (TREM). In addition, the activating Ly49H, NKG2D and natural cytotoxicity receptors (NCRs) on NK cells recognize virus-infected and transformed host cells leading to their elimination.

In recent years, a more complex picture of innate immune receptor functions has emerged. These include cooperation between various innate receptors, including complement system, TLRs, NCRs and other receptors, in ligand recognition and functional regulation as well as activation of adaptive immune responses. Innate immune receptors have now been shown to have a broader expression pattern than previously thought. Various innate immune receptors such as the NCRs have also been described on subpopulations of T cells and NK-like lymphocytes. These recent findings highlight the expanding role of innate immune receptors in various aspects of immunity such as pathogen recognition, inflammation, autoimmunity and tumor immunology. With these recent findings in mind, a complete and up-to-date series of reviews addressing different aspects of innate immune receptor biology is warranted.


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