NK cells play a key role in immune response against HIV infection. These cells can destroy infected cells and contribute to adequate and strong adaptive immune responses, by acting on dendritic, T, B, and even epithelial cells. Increased NK cell activity reflected by higher cytotoxic capacity, IFN-γ and chemokines (CCL3, CCL4, and CCL5) production, has been associated with resistance to HIV infection and delayed AIDS progression, demonstrating the importance of these cells in the antiviral response. Recently, a subpopulation of NK cells with adaptive characteristics has been described and associated with lower HIV viremia and control of infection. These evidences, together with some degree of protection shown in vaccine trials based on boosting NK cell activity, suggest that these cells can be a feasible option for new treatment and vaccination strategies to overcome limitations that, classical vaccination approaches, might have for this virus. This review is focus on the NK cells role during the immune response against HIV, including all the effector mechanisms associated to these cells; in addition, changes including phenotypic, functional and frequency modifications during HIV infection will be pointed, highlighting opportunities to vaccine development based in NK cells effector functions.

Due to the scarcity of therapeutic approaches for COVID-19, we investigated the antiviral and anti-inflammatory properties of curcumin against SARS-CoV-2 using in vitro models. The cytotoxicity of curcumin was evaluated using MTT assay in Vero E6 cells. The antiviral activity of this compound against SARS-CoV-2 was evaluated using four treatment strategies (i. pre–post infection treatment, ii. co-treatment, iii. pre-infection, and iv. post-infection). The D614G strain and Delta variant of SARS-CoV-2 were used, and the viral titer was quantified by plaque assay. The anti-inflammatory effect was evaluated in peripheral blood mononuclear cells (PBMCs) using qPCR and ELISA. By pre–post infection treatment, Curcumin (10 µg/mL) exhibited antiviral effect of 99% and 99.8% against DG614 strain and Delta variant, respectively. Curcumin also inhibited D614G strain by pre-infection and post-infection treatment. In addition, curcumin showed a virucidal effect against D614G strain and Delta variant. Finally, the pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) released by PBMCs triggered by SARS-CoV-2 were decreased after treatment with curcumin. Our results suggest that curcumin affects the SARS-CoV-2 replicative cycle and exhibits virucidal effect with a variant/strain independent antiviral effect and immune-modulatory properties. This is the first study that showed a combined (antiviral/anti-inflammatory) effect of curcumin during SARS-CoV-2 infection. However, additional studies are required to define its use as a treatment for the COVID-19.

Human immunodeficiency virus (HIV) promotes an inflammatory process, leading to the progressive loss of the functional capacity of the immune system. The HIV infection induces alterations in several tissues, but mainly in the gut-associated lymphoid tissue (GALT). However, the degree of GALT deterioration varies among infected individuals. In fact, it has been shown that HIV-controllers, who spontaneously control viral replication, exhibit a lower inflammatory response, and a relative normal frequency and function of most of the immune cells. Inflammasomes are molecular complexes involved in the inflammatory response, being NLRP1, NLRP3, NLRC4, AIM2 and Pyrin inflammasomes, the best characterized so far. These complexes regulate the maturation of cytokines of the IL-1 family, including IL-1β and IL-18. These cytokines have been associated with immune activation and expansion of HIV target cells, promoting viral replication. Interesting, some reports indicate that HIV induces the activation of the NLRP3 inflammasome, but the role of this, and other inflammasomes during HIV infection, especially in GALT, remains unclear. To compare the relative expression of inflammasome components and the proinflammatory response related to their activity, between HIV-progressors and HIV-controllers. GALT biopsies and peripheral blood mononuclear cells (PBMCs) from 15 HIV-controllers and 15 HIV-progressors were obtained. The relative expression of the following inflammasome components were evaluated by RT-PCR: NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β and IL-18. In addition, plasma concentration of IL-18 was evaluated as an indicator of baseline proinflammatory status. Finally, in supernatants of PBMCs in vitro stimulated with inflammasome agonists, the concentrations of IL-1β and IL-18 were quantified by ELISA. HIV-progressors exhibited higher expression of IL-1β, IL-18 and caspase-1 genes in GALT and PBMCs compared with HIV-controllers. In addition, HIV-progressors had also increased expression of ASC in PBMCs. When plasma levels were evaluated, IL-18 was increased in HIV-progressors. Interesting, these patients also showed an increased production of IL-1β in supernatants of PBMCs stimulated in vitro with the agonists of AIM2, NLRP1 and NLRC4 inflammasomes. Finally, the expression of caspase-1, NLRP1, IL-1β and IL-18 in GALT or peripheral blood was correlated with CD4+ T-cell count and viral load. Our results suggest that during HIV-infection, the required signals to induce the expression of different components of the inflammasomes are produced, both in GALT and in periphery. The activation of these molecular complexes could increase the number of target cells, favoring HIV replication and cell death, promoting the disease progression.

Background/Aims: Inflammasomes are multimolecular complexes that regulate caspase-1. They act as sensors for endogenous and exogenous signals, and mediate the processing of pro-IL-1β into its secreted, biologically active form. The NLRP3 inflammasome and IL-1β are particularly interesting because they are required for efficient control of viral infections. Indeed, HIV-1 induces expression of NLRP3 and IL-1β in healthy controls, but not in HIV-1-infected patients. Here we evaluate whether HIV-1 can induce activation of the NLRP3 inflammasome. Methods: Human primary monocyte-derived macrophages were infected with HIV-1 in the absence or presence of classical NLRP3 inflammasome activators, and IL-1β release was assessed by ELISA. Results: HIV-1 initiates the priming signal for NLRP3 inflammasome activation through the NF-κB-associated pathway in human primary monocyte-derived macrophages. Furthermore, priming of NLRP3 activation in response to HIV-1 was independent of the viral envelope, since similar results were observed with HIV-1 and pseudotyped HIV-1 lacking the env gene. Conclusion: Our findings suggest that HIV-1 infection promotes IL-1β secretion by inducing the first signal for NLRP3 inflammasome activation, a phenomenon that may contribute to AIDS progression.