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Annu Rev Biochem. 2007;76:447-80.

Signaling pathways downstream of pattern-recognition receptors and their cross talk.

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Department of Biochemistry, Yonsei University, Seoul 120-749, Republic of Korea.


Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.

[Indexed for MEDLINE]

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