Two-loop model of iADE

Two-loop model of iADE. Ligation of FcγR by infectious DENV-subneutralizing antibody complex induces suppression of innate immune responses by (i) upregulation of negative regulators of pathogen pattern recognition, DAK, Atg5 to Atg12, SARM, and TANK, which subsequently abolish expression of RLR and TLRs and its signaling pathway, resulting in decreased type 1 interferon and proinflammatory cytokine production, which serves to suppress interferon-mediated antiviral responses, and (ii) early activation of IL-10. IL-10 potently activates the SOCS system, suppressing the JAK/STAT signaling pathway and, in turn, the interferon-signaling pathway. IL-10 is known to promote a type Th2 cytokine response, resulting in Th2-type cytokine biasing. These two loops of suppression switch off intracellular antiviral responses in DENV-infected cells under iADE conditions, resulting in the production of high numbers of infectious virions. Tyk2, tyrosine kinase 2; ISRE, interferon-stimulated response element; OAS, 2′,5′-oligoadenylate synthase; PKR, protein kinase R; ISGs, interferon-stimulated genes; GAS, gamma interferon-activated sequence; PGE2, prostaglandin E2.

Publication

How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections . (2010) Sukathida Ubol, et al. Clin Vaccine Immunol. 2010 Dec;17(12):1829-1835. Figure: F1. All organisms Homo sapiens Danio rerio

Disease mentions