THE ROLE OF IL-10 IN FOAMY MACROPHAGE DIFFERENTATION IN TUBERCULOSIS

GENOULA, MELANIE; MARÍN FRANCO, JOSÉ LUIS; DUPONT, MAEVA; KVIATCOVSKY, DENISE; MILILLO, AYELÉN; MORAÑA, EDUARDO JOSE; PALMERO, DOMINGO; BARRIONUEVO, PAULA; BÁRBARA REARTE; ADRIANA FONTANALS; COUGOULE, CÉLINE; VÉROLLET, CHRISTEL; NEYROLLES, OLIVIER; MARIDONNEAU-PARINI, ISABELLE; HERNÁNDEZ-PANDO, ROGELIO; SASIAIN, MARÍA DEL CARMEN; LUGO-VILLARINO, GEANNCARLO; BALBOA, LUCIANA

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS 2017; 2017

The ability of Mycobacterium tuberculosis (Mtb) to persist relies on its numerous immune evasion strategies such as the dysregulation of the lipid metabolism that can lead to foamy macrophage (FM) differentiation. Although FM are proposed to provide an environment which is essential for bacilli to escape from host immune system, the specific host factors leading to FM induction are unknown. We aimed to characterize which host factors may contribute to FM differentiation in the course of Mtb infection. For that we use the acellular fraction of tuberculous pleural effusions (TB-PE) as a source of local factors released during Mtb infection. We treated human macrophages with TB-PE and evaluated the accumulation of lipid bodies (LB) by oil O red staining, cytokines by ELISA, ACAT and STAT-3 by western blot, cholesterol by enzymatic assays, CD36 by FACS, and bacillary loads by colony-forming units assays.PE-TB induced FM differentiation as observed by the increased in lipid bodies (n=), intracellular cholesterol (n=), CD36 expression ?a receptor which mediates lipids uptake- (n=), and ACAT expression ?an enzyme that synthesizes cholesteryl esters- (n=). All these parameters could be prevented after IL-10-depletion of PE-TB in comparison with the depletion of IL-1b, IL-6, IFNg, IL-4, or TNF-a (n=). Also, PE-TB induced the phosphorylation of STAT-3 ?transcription factor that respond to IL-10- (n=) and the expression of CD210 -the receptor for IL-10- (n=). Interestingly, TB-PE promoted the intracellular growth of Mtb in an IL-10 dependent manner (n=10). To confirm the role of IL-10, we evaluated the effect of Mtb lipids on BMDM derived from IL-10 KO or wt mice. IL-10 deficiency reduces LB accumulation induced by Mtb lipids (n=3). In conclusion our results provide evidence for a role of IL-10 in promoting FM differentiation in the context of Mtb infection contributing to our understanding of the host metabolic alterations driven by Mtb.