Trypanosoma cruzi infection modulates innate immune response and lipid metabolism in an experimental model of obesity.

CABALEN ME; CABRAL; ONOFRIO L; GEA S

Buzios

Congreso; XXXIX Congress of the Brazilian Society of Immunology; 2014

Brazilian Society of Immunology

[Abstract ID: 565] IMMUNOLOGY OF INFECTIOUS AND PARASITIC DISEASES (ID) TRYPANOSOMA CRUZI INFECTION MODULATES INNATE IMMUNE RESPONSE AND LIPID METABOLISM IN AN EXPERIMENTAL MODEL OF OBESITY EUGENIA CABALÉN1; MARIA FERNANDA CABRAL1; LUISINA INES ONOFRIO2; MARTA CECILIA ANDRADA1; PATRICIA TORRES BOZZA3; SUSANA GEA2; ROXANA CAROLINA CANO1. 1.FACULTAD DE CIENCIAS QUÍMICAS, UA AREA CS.AGR.ING.BIO Y S CONICET. UNIVERSIDAD CATÓLICA DE CÓRDOBA., CÓRDOBA - ARGENTINA; 2.CIBICI-CONICET-FAC. CIENCIAS QUÍMICAS.UNIVERSIDAD NACIONAL DE CÓRDOBA., CÓRDOBA - ARGENTINA; 3.LABORATÓRIO DE IMUNOFARMACOLOGIA, INSTITUTO OSWALDO CRUZ, FUNDAÇÃO OSWALDO CRUZ., RIO DE JANEIRO - RJ - BRASIL. Keywords: INNATE IMMUNITY;LIPID METABOLISM; OBESITY Abstract Introduction: In LatinAmericaabout 11 millionpeople are infectedwithTrypanozomacruzi (WHO, 2012). Adiposetissueisanimportant target of thisinfectioncontributing to dysregulation in fat and glucosemetabolism. As obesityis a growingepidemicworldwide, ouraimwas to analyzetheinterplaybetweenT.cruziinfection and obesityoninnateimmunity and lipidmetabolism, in a diet-inducedobesitymodel (DIO). Methods and Results: C57BL/6 malemicedivided in control (C), diet (D), diet-infection (DI) and infection (I) groupswerefollowedfor 6 months. D and DI received 13% fatdiet, 5% fructose in water and anintraperitonallydose of streptozotocin (i.p, 8mg/Kg). DI and I wereinfected (i.p) with 500 T. cruzi parasites(Tulahuen). Normal chowdiet (4% of fat) wasgivento C and I groups. Bodyweight and visceral adiposetissue (VAT) weresignificantlyincrease in D groupcompared to C and DI. In DI, infectionamelioratedbothparameters and no significantdifferencewasseenwithgroup I. Bloodtriglycerides (Tg) and cholesterol (Ch)weredeterminedbyenzymaticmethods. Dyslipidemia, givenby a strongincrease in Tg and Ch levelswasfound in D, while a significantdecrease in bothlipidlevelswasseen in DI. Lipoproteinelectrophoreticanalysisshowedanincrease in LDL and VLDL bands in D and DI, suggesting a pro-atherogenic profile. Parasites wereseen in VAT byimmunofluorescence; infiltratingcellswerefound in infectedgroupsand adipocytes of minorsizewereobserved in DI compared to D. IL-6, TNFα, leptin (pg/ml) and adiponectin (APN, ng/ml) wereassayedby ELISA. Significantincreases in lipolyticcytokines, IL-6 and TNFα, werefound in DI group (2699±475; 135±6) compared to D (313±87; 51±2) and I (337±76; 89±9). A markedreduction in APN and leptin levelswasseen in DI (6±1; 9887±1150) in relation to D (12±2; 18890±8000), accordingly to a decrease in bodyweight. As acutephaseproteins (APP) are known to stimulate IL-6 and TNFα production, agaroseelectrophoresiswasperformed, showingan APP increase in DI. Analysis of CD36 in VAT by western blotshowedanincreasedexpression in D and DI, compared to C and I, respectively. MDA quantificationby TBARS (µmol/µg ptna) revealed a stronglipidperoxidation in DI VAT (3.4±1) in comparison to D and I (0.8±0.1;1±0.1). Conclusion: T. cruziinfectionexacerbatesinflammatory response seen in obesemiceresulting in a lipolytic and a pro-atherogenic state. Supportedby SIV-UCC and SECyT-UNC grants.