hiv delays ifn-α production from human plasmacytoid dendritic cells and is associated with syk phosphorylation艾滋病毒延迟ifn-α生产从人类血浆树突细胞和与麦克米兰磷酸化有关.pdfVIP

HIV Delays IFN-a Production from Human Plasmacytoid Dendritic Cells and Is Associated with SYK Phosphorylation 1 1 1 1 2 1,2 Calvin C. Lo , Jordan A. Schwartz , Dylan J. Johnson , Monica Yu , Nasra Aidarus , Shariq Mujib , 2,3 2 2,3 1,2,4 Erika Benko , Martin Hyrcza , Colin Kovacs , Mario A. Ostrowski * 1 Department of Immunology, University of Toronto, Toronto, Ontario, Canada, 2 Department of Medicine, University of Toronto, Toronto, Ontario, Canada, 3 Maple Leaf Medical Clinic, Toronto, Ontario, Canada, 4 Li Ka Shing Institute, St. Michael’s Hospital, Toronto, Ontario, Canada Abstract Plasmacytoid dendritic cells (pDC) are the major producers of type I interferons (IFNs) in humans and rapidly produce IFN- a in response to virus exposure. Although HIV infection is associated with pDC activation, it is unclear why the innate immune response is unable to effectively control viral replication. We systematically compared the effect of HIV, Influenza, Sendai, and HSV-2 at similar target cell multiplicity of infection (M.O.I.) on human pDC function. We found that Influenza, Sendai, HSV-2 and imiquimod are able to rapidly induce IFN-a production within 4 hours to maximal levels, whereas HIV had a delayed induction that was maximal only after 24 hours. In addition, maximal IFN-a induction by HIV was at least 10 fold less than that of the other viruses in the panel. HIV also induced less TNF-a and MIP-1b but similar levels of IP-10 compared to other viruses, which was also mirrored by delayed upregulation of pDC activation markers CD83 and CD86. BDCA-2 has