Receptors and signaling in the innate immune system

Purpose of review In this review, we highlight the current conceptual framework for innate immunity. Recent findings We highlight the interactions of pattern recognition receptors, including Toll-like receptors, non-Toll-like membrane-bound pattern recognition receptors, and intracellular sensors neuronal apoptosis inhibitory protein, CIITA, HET-E, and TP1-leucine-rich repeat (NLRs). Toll-like receptors recognize pathogen-associated molecular patterns and activate signaling pathways that induce the expression of immune and proinflammatory genes. Toll-like receptors use overlapping signaling pathways that largely depend on intracellular adaptor molecules. Recent evidence suggests that non-Toll-like membrane-bound pattern recognition receptors such as dectin-1, CD36, and CD14 collaborate with Toll-like receptors in pathogen-associated molecular pattern recognition or use Toll-like receptors as signaling partners. NLRs, whose function is to detect intracellular pathogen-associated molecular patterns, also share the signaling pathways used by some Toll-like receptors, suggesting cooperation and synergy between NLRs and Toll-like receptors. Summary The integration of signals generated from Toll-like receptors and other non-Toll-like receptors might instruct the nature and outcome of the immune response to a particular pathogen. This has implications for inflammatory diseases and host defense, because understanding these precise interactions presents novel targets for specific therapeutics.