Genetic and functional characterization of NLRP-3 in lymphocytes and monocytes from chronically infected HIV-1 individuals

Abstract

The NLRP3-inflammasome was described as a complex present in the cytosol of innate immune cells that leads to the activation of an inflammatory caspase-1 protease with consequent cleavage and release of the pro-inflammatory cytokines IL-1² and IL-18 and also Gasdermin-D which is important to the cell death process by pyroptosis, which in the context of HIV infection may influence both the chronic inflammation and T CD4+ lymphocytes depletion. Besides, it was demonstrated that the NLRP3 can act in a inflammasome-independent way as co-transcriptional factor to IL4 in T CD4+ leading to a Th2 profile, which in HIV-1 chronically infected individuals may be related to a worse prognosis considering that the predominant polarization to a Th2 response is associated to Aids progression. In this context, the role of NLRP3 in Th2 polarization is being currently investigated. Therefore, we believe that in HIV-1 infection the activation of NLRP3 occurs also in lymphoid cells with a different effect according to the cell type, contributing to the pathogenesis of the disease. Our preliminary genotyping results suggests that NLRP3 has an important role in the response of infected individuals. Besides, we could observe a differential expression of inflammasome components in lymphocytes from chronically infected individuals. We believe that the NLRP3 may also exert an important role in B lymphocytes activation and antibody production depending on the stimulus, deserving to be deeply investigated. (AU)