Avaliação da coexpressão NLRP3/ASC do inflamassoma e sua relação com inflamação e atividade microbicida no espectro clínico da hanseníase

Abstract

Hansen’s disease is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), whose clinical diversity reflects marked differences in the host immune response. The polarization between paucibacillary (PB) and multibacillary (MB) forms involves complex interactions between innate and adaptive immunity, including inflammatory pathways that remain incompletely understood. In this context, the present study aimed to evaluate the expression pattern of the NLRP3/ASC complex in patients with leprosy presenting different clinical forms of the disease. This was an observational, cross-sectional study using peripheral blood mononuclear cells (PBMCs) stimulated in vitro with M. leprae antigen, followed by flow cytometric analysis to characterize monocyte-derived macrophages, including the coexpression of NLRP3 and ASC and intracellular IL-1β production. Stimulated T lymphocytes (LTCD4+CD45RO+ and LTCD8+CD45RO+) were further evaluated for IFN-γ and IL-10 production, and nitric oxide (NO) levels were quantified in culture supernatants. MB patients exhibited a significantly increased percentage of CD14+HLA-DR+NLRP3+ASC+ macrophages and higher mean fluorescence intensity (MFI) for IL-1β in these cells. A positive correlation was observed between the bacillary index and the frequency of these double-positive cells, as well as a negative correlation between complex expression and NO production. Differently from MB patients, the PB group exhibited a higher stimulation index for NO production in response to antigenic stimuli, along with increased IFN-γ production and a significantly higher IFN-γ/IL-10 ratio in T lymphocytes. A negative correlation between bacillary load and NO production activity was also identified. Collectively, these findings indicate that although the MB form is associated with increased expression of structural components of the inflammasome and enhanced IL-1β production, bacillary containment appears to depend on more efficient microbicidal mechanisms, such as NO production and a predominant TH1 microenvironment, characteristic of PB patients. These results highlight a dissociation between the intensity of inflammatory signaling and effective infection control in the MB form.