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

Using real time quantitative assay, we have shown significant upregulation of TRAIL gene expression in avian influenza (H5N1) infected macrophages [43] . Similarly, SARS-CoV infected DC also showed a "killer DC' phenotype with high expression of TRAIL (Fig. 4) . Comparing the two studies, the level of TRAIL expression in SARS-CoV infected adult DCs (~300 copies/10 4 β actin genes) was lower than that in H5N1 infected adult macrophages (~1800 copies/10 4 β actin genes). TRAIL expression in SARS-CoV infected CB DCs was the highest (~5000 copies/10 4 β actin genes). Further investigation is needed to confirm the cytotoxic function of SARS-CoV infected DCs on immune cells. Based on the possible DC migration induced by chemokines and the role of TRAIL in inducing lymphocyte apoptosis, our findings may explain the white pulp atrophy in the spleen and lymphoid depletion in lymph nodes of SARS patients. The mechanism involved in children may be more complicated and it is important to determine if the CB DCs are functionally immature in spite of the high expression of chemokines, CCRs and TRAIL. More recently, TRAIL expression is also reported to be upregulated after the binding of HIV to TLR-7 [44] or activation of TLR-8 [45] . Hence the high TRAIL expression in SARS-infected CB DCs may also be related to their TLR-8 expression.