Sunday, May 19, 2024
5/19/2024
DESCRIPTION (provided by applicant): Neisseria gonorrhoeae (gonococci, GC) causes gonorrhea and pelvic inflammatory disease (PID). Gonorrhea probably facilitates infection with HIV-1 through the activation of host immune cells, which are targeted by HIV. Recently, we demonstrated that pre-incubation of human dendritic cells (DCs) with GC resulted in a dramatically increased DC infection by HIV-1. This outcome should be due to enhancement of either HIV entry or in viral replication in DCs. Pre-incubation of DCs with GC did not significantly up-regulate expression of HIV receptor molecules such as CD4, CCR5, CXCR4, and DC-SIGN, indicating that HIV infection enhancement in DCs might be due to an increase in viral replication. When GC enters the hosts, it releases components, such as lipopolysaccharide (LPS), lipoprotein H.8, porin and peptidoglycan (PGN), which can activate Toll-like receptors (TLRs). Bacterial components including GC products have implicated the capacity to stimulate HIV replication and production through TLRs. Therefore, in the proposed research, we will first confirm that GC promotes an enhancement of HIV infection in DCs. Then, we hypothesize that GC-mediated enhancement of HIV infection in DCs may be achieved through the following event: GC enters the host and releases multiple stimuli such as LPS and PGN that activate host cells through TLRs. Consequently, GC leads to the enhancement of HIV infection in DCs during co-infection. Therefore, we have designed two specific aims to investigate this event. 1. Determine whether GC enhances HIV-1 infection in dendritic cells. 2. Elucidate how GC stimulates the replication of HIV-1 in dendritic cells through Toll-like receptors. The outcome of this proposal provides one potential mechanism to explain why HIV-positive patients with gonorrhea have an increased viral load. This knowledge will help us to understand why we need to aggressively treat STDs in AIDS patients.
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