Trypanosoma cruzi modulates LPS maturation process of DC in vitro

PONCINI C.; ALBA SOTO C.; SOLANA M.; BATALLA E.; GONZÁLEZ CAPPA SM

Rio de Janeiro

Congreso; 13th International Congress of Immunology; 2007

Previously we reported the effects of trypomastigotes (Tp) of a virulent strain (RA) on APC, in a murine infection model. To better understand mechanisms responsible of these alterations, in vitro cocultures of bone marrow dendritic cells (BMDC) with Tp were carried out. Infection but not apoptosis was detected. Maturation phenotypes after treating these cells with LPS, Tp and Tp+LPS were studied. By flow cytometry, we analyzed the surface expression profiles of MHCII, costimulatory molecules and dextran uptake. By ELISA, we characterized secretion of pro- anti- inflammatory cytokines. Tp failed to increase MHCII expression and inhibited that induced by LPS (MFI±SE, C: 119±27, LPS: 186±40*, Tp: 111±22, Tp+LPS: 131±25, n=11, *p<0.01). Tp failed to modify CD40, CD80 and CD86 MFI with or without LPS (CD40: 34±4, 61±10*, 45±6, 70±13**; CD80: 57±13, 105±27**, 62±14, 103±30*; CD86: 178±48, 229±50*, 187±45, 210±49*, n=7, *p<0.05, **p<0.01).  A drop in FITC-Dextran uptake was seen after treatment with LPS (% positive FITC cells±ES, C: 33±7, LPS: 19±4*, Tp: 45±4, n=3, *p<0.05). Tp failed to affect control basal amount of IL-10 and IL-6, as seen with LPS (24hs, p<0.05, p<0.001). Eventhought, Tp synergized the IL-10(pg/ml) production by LPS (C: 7±3, Tp: 24±5, LPS: 473±101*, LPS+Tp: 762±100**; n=4) picking at 12hs (p<0.01). Synergism is maintained at least 24hs (p<0.05). Preliminary results suggest that Tp inhibits lymphocyte stimulatory activity of DC pretreated with LPS in a MLR. Together, results suggest that even Tp RA are deficient inducer, they are efficient modulators of immune response, probably towards to a tolerogenic profile.