Chronic Trypanosoma cruziinfection potentiates adipose tissue macrophage polarization toward an anti-inflammatory M2 phenotype and contributes to diabetes progression in a dietinduced obesity model

CABALEN, ME; CABRAL, MF; SANMARCO, LM; ANDRADA, MC; ONOFRIO, L; PONCE, NE; AOKI, MP; GEA, SUSANA; CANO, RC

ONCOTARGET

Oncotarget eiditorial

Año: 2016

Chronic obesity and Chagas disease (caused by the protozoan Trypanosoma cruzi) represent serious public health concerns. The interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has  not  been  entirely  explored.  A  novel  diet-induced  obesity  model  (DIO)  was developed  in  C57BL/6  wild  type  mice  to  examine  the  effect  of  chronic  infection (DIO+I) on metabolic parameters and on obesity-related disorders. Dyslipidemia, hyperleptinemia,  and  cardiac/hepatic  steatosis  were  strongly  developed  in  DIO mice. Strikingly, although these metabolic alterations were collectively improved by  infection,  plasmatic  apoB100  levels  remain  significantly  increased  in  DIO+I, suggesting the presence of pro-atherogenic small and dense LDL particles. Moreover, acute insulin resistance followed by chronic hyperglycemia with hypoinsulinemia was found, evidencing an infection-related-diabetes progression. These lipid and glucose metabolic changes seemed to be highly dependent on TLR4 expression since TLR4-/- mice were protected from obesity and its complications. Notably, chronic infection promoted a strong increase in MCP-1 producing macrophages with a M2 (F4/80+CD11c-CD206+) phenotype associated to oxidative stress in visceral adipose tissue of DIO+I mice. Importantly, infection reduced lipid content but intensified inflammatory infiltrates in target tissues. Thus, parasite persistence in an obesogenic environment and the resulting host immunometabolic dysregulation may contribute to diabetes/atherosclerosis progression