Interleukin 18 (IL-18) and IL-3 in Extracellular Vesicles: Biomarkers for Durable Elite Control of HIV-1

Abstract

Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.

Keywords: HIV; cytokines; elite controllers; extracellular vesicles; functional cure.

Figure 1.

Heap map of the relative cytokine levels associated with extracellular vesicles. The levels of cytokines for each study group are represented as the standardized mean of each group as a comparator for each cytokine. Abbreviations: ART, antiretroviral therapy; EC, elite controller.

Figure 2.

Pathways analysis of key distinguishing cytokines: IL-18 and IL-3/TRAIL. My Pathway analysis in ingenuity pathway analysis was used to link (A) IL-18, the cytokine best distinguishing elite controllers from antiretroviral therapy treated, and (B) IL-3/TRAIL, the cytokines best distinguishing persistent from transient controllers, to top canonical pathways and downstream biological functions. Abbreviations: CP, canonical pathways; Fx, biological functions; IL, interleukin; TRAIL, tumor necrosis factor-related apoptosis inducing ligand.