title: Differential response of primary and immortalized CD4+ T cells to Neisseria gonorrhoeae-induced cytokines determines the effect on HIV-1 replication.
abstract: To compare the effect of gonococcal co-infection on immortalized versus primary CD4(+) T cells the Jurkat cell line or freshly isolated human CD4(+) T cells were infected with the HIV-1 X4 strain NL4-3. These cells were exposed to whole gonococci, supernatants from gonococcal-infected PBMCs, or N. gonorrhoeae-induced cytokines at varying levels. Supernatants from gonococcal-infected PBMCs stimulated HIV-1 replication in Jurkat cells while effectively inhibiting HIV-1 replication in primary CD4(+) T cells. ELISA-based analyses revealed that the gonococcal-induced supernatants contained high levels of proinflammatory cytokines that promote HIV-1 replication, as well as the HIV-inhibitory IFNα. While all the T cells responded to the HIV-stimulatory cytokines, albeit to differing degrees, the Jurkat cells were refractory to IFNα. Combined, these results indicate that N. gonorrhoeae elicits immune-modulating cytokines that both activate and inhibit HIV-production; the outcome of co-infection depending upon the balance between these opposing signals.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Dobson-Belaire
authors.forename: Alan
authors.initials: A
authors.lastname: Cochrane
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000382:microbiology; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha