Signaling pathways downstream of pattern-recognition receptors and their cross talk.
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.
Lee
Myeong Sup
MS
Department of Biochemistry, Yonsei University, Seoul 120-749, Republic of Korea. myeongsup.lee@gmail.com
Kim
Young-Joon
YJ
D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D007107:Immune System / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000235:genetics / Q000378:metabolism; D053472:Nod Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000099181:Dectin-1
D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D016753:Interleukin-10; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D053472:Nod Signaling Adaptor Proteins; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D000099181:Dectin-1