IL-10 PROMOTES LIPID BODIES ACCUMULATION WITHIN MACROPHAGES IN THE CONTEXT OF TUBERCULOSIS

BALBOA L; KVIATCOVSKY D; GENOULA M; MORAÑA E; INWENTARZ S; GONZÁLEZ MONTANER P; SASIAIN MC

Buenos Aires

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2015

LASID SAI FAIC

The ability of Mycobacterium tuberculosis (Mtb) to persist and cause tuberculosis relies on its numerous immune evasion strategies, including the dysregulation of the lipid metabolism in macrophages inducing foamy macrophages (FM) formation. So far the specific host factors leading to FM induction are unknown. We characterized different macrophage profiles, M2, M1, M2a, and M2c, for their propensity to accumulate lipid bodies (LB) during Mtb infection. Macrophage profiles were generated and exposed to pleural effusions (PE) from tuberculous patients (TB-PE) or heart failure patients (HF-PE). LB accumulation was evaluated by oil red and BODIPY staining, IL-10 and TNF-a by ELISA, pSTAT-3 by FACS and western blot, ROS production by DHR labelling, and antigen presenting capacity by CFSE-labelled lymphocytes determination.Unlike HF-PE, TB-PE induced LB in M2, M2c and M1 (n=8). M2a did not accumulate LB (n=8). As high levels of IL-10 and TNF-a were found in PE-TB (n=5), we evaluated the effect of depleting them. Unlike TNF-a, IL-10 depletion prevented FM differentiation (n=8). Besides, PE-TB or IL-10 addition induced CD36 expression, which mediates lipids uptake, and pSTAT-3 levels, which governs the M2c program (n=5); moreover pSTAT-3 inhibition prevented LB accumulation (n=3). In terms of the function, TB-PE impaired ROS production and IFNg-producing CD4 cells proliferation induced by M1; M2a were not affected and M2c lacked both functions (n=4). So macrophage profiles differ in their propensity to accumulate LB, process which requires the activation of the IL-10/STAT-3 axis and results in an immunesuppressive phenotype, impairing the host immune response against Mtb.