Executive Summary : | A model of DC dysfunction during advanced stage of HIV disease, when the patients are more prone to opportunistic infections, could be proposed. Chronic TLR stimulation of DCs potently induces upregulation of negative regulators like SOCS-1 or SHP-1 which may have a profound negative effect either on the JAK-STAT or TLR-NF-kB pathways that ultimately exerts inhibitory effects on cytokine production as well as down-modulation of effective T cell response. Results may have important clinical implications and suggest the design of new generation preventive or therapeutic vaccines based on silencing of one or more of these negative regulators after studying the precise contribution of each of these factors at transcriptional level. Further elucidation of more genes involved in cytokine signaling could help in revealing pathways used by HIV to drive its spread and to identify therapeutic strategies to bias DC biology towards immunity. Understanding DC dysregulation as per HIV disease pattern will pave the way to use of novel therapeutics in the form immune-modulators that may lead to proper DC stimulation which may revert the tolerogenic environment for better handling of bacterial onslot, imminent in this stage of disease. |