Improved induced innate immune response after cART initiation in people with HIV

Abstract

IntroductionImpairment of the innate immune function may contribute to the increased risk of bacterial and viral infections in people with HIV (PWH). In this study we aimed to investigate the induced innate immune responses in PWH prior to and after initiation of combinational antiretroviral therapy (cART). Furthermore, we aimed to investigate if the induced innate immune responses before initiation of cART were associated with CD4+ T-cell recovery one year after initiating cART.Material and methodThe induced innate immune response was assessed by the TruCulture® whole blood technique in 32 PWH before cART initiation and after 1, 6 and 12 months. To mimic bacterial and viral infections we used a panel of three stimuli (lipopolysaccharide (LPS), resiquimod (R848), and polyinosinic:polycytidylic acid (Poly I:C)) to stimulate the extracellular Toll-like receptor (TLR) 4 and the intracellular TLR7/8 and TLR3, respectively. The following cytokine responses were analyzed by Luminex 200: Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p40, IL17A, Interferon (IFN)-α, and IFN-γ.ResultsAt baseline PWH with nadir CD4+ T-cell count <350 cell/µL had lower levels of LPS-, R848-, and Poly I:C-induced IL-6 and IFN-γ, LPS- and R848-induced TNF-α and IL-12, LPS induced IL-1b, and R848-induced IL-10 than PWH with nadir CD4+ T-cell count >350 cells/µL. The majority (>50%) had induced cytokine concentrations below the reference intervals at baseline which was most pronounced for the LPS- and Poly I:C-induced responses. The induced responses in the whole population improved after 12 months of cART, and more PWH had induced cytokine concentrations within the reference intervals after 12 months. However, the majority of PWH still had LPS-induced INF-α, INF-γ and Poly I:C-induced TNF-α and IL-6 below the reference interval. The induced innate immune responses before cART initiation were not associated with the CD4+ T-cell recovery after 12 months of cART.ConclusionThe innate immune response was impaired in PWH, with a more pronounced impairment in PWH with low nadir CD4+ T-cell count. Initiation of cART improved the innate immune response, but compared to the reference intervals, some impairment remained in PWH without viral replication.

Prediction of herpes virus infections after solid organ transplantation: a prospective study of immune function

“…The TruCulture® assay has been described previously ( 15 , 16 , 24 ). In brief, 1 mL of whole blood was transferred into four TruCulture® tubes (Myriad RBM, Autin, TX, USA) within one hour of sampling.…”

“…However, these studies only assessed CMV-specific immunity. Interestingly, a new commercially available and highly standardized method (TruCulture®) to asses overall immune function has been investigated in other settings and may be used in SOT recipients ( 15 – 17 ). We hypothesized that individual immune function contributes to the observed differences in the risk of herpes virus infections.…”

Whole blood stimulation as a tool for studying the human immune system

“…Combining whole blood stimulation with longitudinal sampling of patients has been used to monitor changes in responsiveness over time with regard to disease progression and treatment‐induced effects. For example, longitudinal sampling before and during treatment was performed to study innate immune function during different cancer treatments [63] and combinational antiretroviral therapy in HIV [64]. Further, longitudinally sampling COVID‐19 patients from admission to the hospital until dismissal (or death) revealed that lower release of IL‐1β upon LPS as well as IL‐12 and IL‐17A upon R848 stimulation at admission were associated with more severe disease at peak severity [65].…”