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; IV Lasid Meeting, LXII SAI, II French Argentinean Immunology Meeting,; 2015

Objective: To characterize different macrophage profiles for their propensity to accumulate lipid bodies during Mtb infection. Monocyte- derived macrophages from healthy donors were polarized to M1, M2, M2a and M2c and exposed to pleural effusions from TB and heart failure (control) patients to determine: i) Lipid bodies formation by ORO staining / BODIPY labelling / Cholesterol ii) ROS production by DHR labelling iii) Antigen presenting capacity by CFSE-labelled lymphocytes determination and iv) Bacillary loads by CFU. Results: M2c showed high propensity to accumulate lipid bodies after exposition to TB-pleural effusions. The depletion of IL-10 prevents differentiation into foamy macrophages after TB-PE exposition. TB-PE induces CD36 expression unlike control-PE. The addition of IL-10 promotes CD36 upregulation. TB-PE depleted of IL-10 does not induce CD36 upregulation. The addition of Cucurbitacin (STAT-3 inhibitor) prevents differentiation into foamy macrophages after TB-PE exposition. ROS production by M2a in response to Mtb was not affected by TB-PE addition. M2c did not induced ROS production in response to Mtb. ROS production by M1 in response to Mtb was impaired by TB-PE. TB-PE impaired the proliferation of IFNgpos CD4 cells induced by M1. TB-PE increased the bacillary loads recovered from M2a , M2c and M1. The increase of the bacillary loads induced by TB-PE depended on IL-10 in M2c and M1.Conclusions: Macrophage profiles differ in their propensity to accumulate lipid bodies, 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.