Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells

Law, Helen KW; Cheung, Chung Yan; Sia, Sin Fun; Chan, Yuk On; Peiris, JS Malik; Lau, Yu Lung

In the current study, we focused on the receptor responses in SARS-CoV infected DCs and compared adult and cord blood (CB) DCs to establish possible explanation for the age dependent severity of SARS. DCs express a wide range of receptors for the recognition of conserved pathogen patterns as well as the induction of subsequent immune responses. Some Toll like receptors (TLRs) are expressed on the cell surface (TLR-1, TLR-2, TLR-4, TLR-5, TLR-6, TLR-10) while some are located within intracellular compartments (TLR-3, TLR-7, TLR-8, TLR-9) [9] . They are differentially expressed in different DC subsets and are modulated in response to a variety of stimuli [10, 11] . Viral proteins may bind to TLR-2 or TLR-4, single stranded RNA binds to TLR-7 and TLR-8, and double stranded RNA binds TLR-3 while viral DNA binds to TLR-9. The binding of ligands to TLRs may trigger downstream signaling pathways that are involved in both the cytokine release during the primary induction of inflammation and secondary activation of anti-inflammatory mechanisms [12] . Cross talks between TLRs are common and the formation of TLR heterodimers allows a higher level of complexity in ligand-receptor binding and subsequent signaling.