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.
Highlights
Co-infection between HIV and other sexually transmitted infections (STIs) is an area of intense interest because of the impact that STIs have on the global spread of HIV
The HIV-stimulatory effect of N. gonorrhoeae was less apparent in the co-infected primary CD4+ T cells at the tested multiplicity of infection (MOI) of 10 bacteria per cell, the effect did still trend towards stimulation (Fig 1B and D)
We have recently established that N. gonorrhoeae elicits a potent plasmacytoid dendritic cell response in mixed primary peripheral blood mononuclear cells (PBMCs) cultures, leading to their production of sufficient IFNa to inhibit HIV-1 replication [7]
Summary
Co-infection between HIV and other sexually transmitted infections (STIs) is an area of intense interest because of the impact that STIs have on the global spread of HIV. The lack of a non-human in vivo model that accurately reflects what occurs during co-infection has led to a reliance on in vitro models to study these interactions. This has yielded conflicting, sometimes confusing results that affect confidence in the interpretations. One of the better-studied co-infections is that involving Neisseria gonorrhoeae and HIV-1. While the ultimate effect of N. gonorrhoeae on HIV-1 replication in vivo will depend upon the cumulative effect of activating and inhibitory stimuli, these conflicting observations have made it difficult to dissect the impact of N. gonorrhoeae infection on viral expression at a cellular level
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