CONICET | Buscador de Institutos y Recursos Humanos

T. cruzi infection is characterized by tissue damage which may be a direct effect of the parasite or the aggressive immune response displayed by the host. Indeed, there are differences among mouse strains in the control of both parasite replication and inflammatory response. Infected B6 strain develop a Th1-type response that controls the parasite replication but they are unable to generate Treg cells and to control the inflammatory pathology. Conversely, infection of BALB/c mice induces the development of Treg and a Th2-type response unable to control the intracellular parasite replication. Both mice strains upregulate the activity of indoleamine 2,3 dioxigenase (IDO), critical for host resistant, and express responsive aryl hydrocarbon receptor (AhR) alleles. AhR is a ligand-activated transcription factor expressed in immune cells that plays a role in regulating Treg and Th17 differentiation and triggers IDO activity in DC. Our hypothesis is that the different immune responses displayed by B6 y BALB/c mice to T. cruzi infection can be explained in part by the regulation of AhR expression. To compare AhR expression BALB/c and B6 mice were ip injected with 500 and 3000 trypomastigotes respectively, and the AhR expression was determined in spleen mononuclear cells (SMC) by Quantitative Real Time PCR (qPCR), Western Blot and flow cytometry. qPCR results showed that AhR expression in non-infected (NI) B6 mice was 3 times higher than in NI BALB/c mice. T. cruzi infection induced, at day 7 pi, a transient and significant upregulation (2-fold increase) of AhR expression in Balb/c mice whereas in B6 mice AhR mRNA was markedly reduced (2.5 fold decrease). At protein level, an upregulation of AhR expression was observed at day 17 pi showing 4- and 42-fold induction in SMC from BALB/c and B6, respectively. AhR is naturally more expressed in immune cells from B6 than Balb/c mice and T. cruzi infection modulate differentially their expression in both mice strains.