CERBAN FABIO MARCELO
Congresos y reuniones científicas
Título:
Intracellular mediators involved in macrophage polarization during Trypanosoma cruzi infection and its role in parasite survival.
Autor/es:
JORGE ROJAS M; RUTH BAIGORRI; CINTHIA STEMPIN; CERBAN F
Reunión:
Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2015
Resumen:
Previously, we evaluated the role of mammalian target of rapamycin (mTOR) in macrophage polarization and parasite replication. By inhibition of mTOR activity, parasite replication decreased and it is accompanied by a down-regulation of arginase activity and expression and increased IL-12 production. Surprisingly, activity and expression of iNOS was also found down-regulated during pretreatment with rapamycin. Therefore, the aim of this work was to determine alternative mechanisms activated during inhibition of mTOR, involved in reducing parasite replication. To do that, we evaluated inflammatory transcription factors that are activated during T. cruzi infection. Bone marrow derived macrophages (BMDM) infected in vitro showed increased of STAT-1 phosphorylation and IRF-5 expression at 15', 30', 1h and 2h after infection, with a peak at 30 min. Later, we evaluate the ability of BMDM to modify T cell proliferation in response to unspecific stimulation. Total splenocytes were labeled with CFSE and co-cultured with rapamycin pre-treated and infected BMDM. We observed lower proliferation in splenocytes co-cultured with rapamycin pre-treated and T. cruzi-infected BMDM. Next, we analyzed the expression of co-inhibitory and co-stimulatory molecules in these BMDM. We found that PD-L1, PD-L2 and CD86 were down-regulated. Besides, we decided to evaluate ROS production as a possible mechanism responsible for the reduced parasite load in rapamycin pre-treated and infected BMDM. We found, that as well as iNOS, ROS production is not involved. Although it is still not elucidated the microbicide mechanism/s activated during mTOR inhibition, our results showed that mTOR pathway play an important role during T. cruzi infection.