MODULATION OF METABOLIC PATHWAYS SIGNALING IN MACROPHAGES INFECTED WITH TRYPANOSOMA CRUZI INDUCE M1-LIKE PHENOTYPES THAT CONTROLS PARASITE SURVIVAL

BRUGO, MARÍA B.; ROJAS MARQUEZ, JORGE D.; ANA, YAMILE; STEMPIN, CINTHIA C.; CERBAN, FABIO M.

Mar del Plata

Congreso; LXVI reunión anual de la Sociedad Argentina de Inmunología (SAI); 2018

SAI

Macrophages (Mo) play a key role in the control of intracellular T.FUX]L JURZWK +RZHYHU SDUDVLWH VXEYHUWV 0R SRODUL]DWLRQ WKURXJKPRGXODWLRQRIVHYHUDOVLJQDOLQJSDWKZD\VWRIDYRULWVVXUYLYDO,QWKLVVWXG\ZHIRFXVHGLQPHWDEROLFSDWKZD\V P725DQG$03.DQGLWV UROH GXULQJ7 FUX]L LQIHFWLRQ LQ0R:H KDYH SUHYLRXVO\ VKRZQWKDWP725 SDWKZD\ LV DFWLYDWHG E\7 FUX]L DQGWKDW LWV LQKLELWLRQdecreased parasite replication in Mo. We observed that, RapamyFLQ 5DS DQP725LQKLELWRUSUHWUHDWHGDQG7 FUX]LLQIHFWHG0RVKRZHGUHGXFHGQLWULFR[LGH12SURGXFWLRQDQGL126H[SUHVVLRQ+RZHYHU WKRVH PDFURSKDJHV FRXOG FRQWURO SDUDVLWH UHSOLFDWLRQWKURXJK DFWLYDWLRQ RI GLIIHUHQW LQÁDPPDWRU\ PHFKDQLVP ,QGHHGWKRVH0R VKRZHG D VLJQLÀFDQW LQFUHDVH LQ 1/53 LQÁDPPDVRPHUHFHSWRUDQG,/ћSURGXFWLRQ*LYHQWKDWLQÁDPPDVRPHFRXOGHPSOR\WKHPLWRFKRQGULDDVSODWIRUPRIDVVHPEO\ZHIRXQGDVLJQLÀcantly increase in mitochondrial ROS (mtROS) production (3 and 6hSL7RHYDOXDWHWKHUHOHYDQFHRIPW526DQGLQÁDPPDVRPHDFWLYDWLRQ%RQH0DUURZ'HULYHG0DFURSKDJHV%0'0ZHUHWUHDWHGZLWKDPI (NADPH oxidase inhibitor), or mitoTEMPO (superoxide species>PW526@VFDYHQJHURU&$FDWKHSVLQ%LQKLELWRUDQGWKHQLQIHFWHGZLWK7FUX]L:HREVHUYHGWKDWPW526DQGFDWKHSVLQ%DQLQÁDPPDVRPHDFWLYDWRULQKLELWLRQLQGXFHVLJQLÀFDQWO\KLJKHUSDUDVLWHORDG S2QWKHRWKHUKDQGZHIRXQGWKDWSUHWUHDWPHQWZLWK0HWIRUPLQ0HWDQ$03.DFWLYDWRULQLQIHFWHG0RVKRZHGDdecreased in parasite replication (p<0.05). To determinate Mo actiYDWLRQZHHYDOXDWH$UJLQDVHDQGL126EDODQFHLQ0HWSUHWUHDWHGand infected Mo. We found decreased Arginase activity and expression and increased NO production and INOS expression, respect tocontrol Mo. This may indicate that Met induces a M1-like phenotype,capable to control parasite replication. Taking together, these resultsVXJJHVWWKDW7FUX]LUHSOLFDWLRQFRXOGEHFRQWUROOHGWKURXJKPRGXODWLRQRIPHWDEROLFSDWKZD\VVXFKDVP725DQG$03.WKRVHDOORZVPDFURSKDJHVSRODUL]H0OLNHSKHQRW\SHV