MANNOSE RECEPTOR RECYCLING FAVORS ARGINASE INDUCTION AND T. CRUZI SURVIVAL IN MACROPHAGES.

GARRIDO VV, DULGERIAN LR, STEMPIN CC, CERBAN FM.

Congreso; I Congreso Franco Argentino de Inmunología.; 2010

Previously we demonstrated that the iNOS/arginase balance was biased towards arginase in Trypanosoma cruzi infected macrophages (Mo) pre-incubated with mannose-BSA (man-BSA, mannose receptor (MR) specific ligand). Moreover, intracellular parasite growth was increased. In addition, the study of MAP kinase intracellular signals showed that pre-incubation with man-BSA but not mannan, induced down-regulation of p-JNK and p-p44/p42 and up-regulation of p-p38 MAPK in T. cruzi infected J774 cells. These results are coincident with previous data published by our group in T. cruzi infected Mo pre-incubated with Cruzipain (Cz). These results suggested that man-BSA and Cz might interact with the same receptor (MR). Moreover, we showed that pre-incubation with man-BSA induced MR up-regulation or increased MR recycling on Mo surface. In this work, we study MR behavior in Cz-Mo interaction. J774 cells were treated with Cz during 2h and then incubated with man-BSA-FITC for 20 minutes. Flow cytometry analysis showed that Cz increased the percentage of FITC+ cells. Therefore, Cz might interact with MR in the same way that man-BSA. Then, we studied whether Cz or man-BSA induced MR up-regulation or increased MR recycling. Therefore, J774 cells were incubated for 1, 2 or 3 hs with man-BSA-FITC at 4 C or room temperature. Then, cells were treated with acid washed and were analyzed by flow cytometry and confocal microscopy. This study showed that the interaction between Cz or man-BSA with MR induced MR increased recycling. Later, we studied the MR behavior during T. cruzi infection in vivo.  MR was up regulated in F4/80+ cells from T. cruzi infected mice at 13 and 15 days post infection. Besides, we investigated the effect of MR blocking antibody in T. cruzi infected peritoneal Mo. Arginase activity (p