Interaction of Signaling Lymphocytic Activation Molecule Family 1 (SLAMF1) receptor with Trypanosoma cruzi is strain-dependent and affects NADPH oxidase expression and activity

摘要

Chagas disease, caused by Trypanosoma cruzi, is characterized by an acute phase, with low mortality, and after many years without any sign of disease, patients develop a symptomatic chronic phase, characterized by cardiomyopathy and/or digestive mega syndromes. These differences have been attributed to the high genetic variability of this parasite. We have shown that the receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal T. cruzi Y strain. Here we studied in detail the immunopathogenic role of SLAMF1 using 6 genetically diverse strains of T. cruzi using in vitro and in vivo approaches. Our results indicate an important role of SLAMF1 in T. cruzi infection which is parasite strain-dependent. We found that parasites interact with SLAMF1 in macrophages affecting NADPH oxidase (NOX2) expression and reactive oxygen species (ROS) production 5 out of 6 strains tested. Y and VFRA strains showed a divergent behavior in vitro and the role of SLAMF1 in the in vivo infection was also strikingly different. The Y strain caused 70% mortality in BALB/c mice but not in Slamf1-/- mice. The proinflammatory response was stronger in the last, suggesting that SLAMF1 was repressing protective immune responses of mice infected with the Y strain. In contrast, for VFRA, SLAMF1 deficiency resulted in 100% survival of BALB/c mice, without major changes in the immune response in the absence of SLAMF1. Thus, the results indicate that SLAMF1 receptor interacts with T. cruzi, affecting parasite replication and ROS production in macrophages as well as the adaptive immune response in mice in a parasite strain-dependent manner. Future studies will focus in understanding the immunopathogenic role of SLAMF1 during T. cruzi infection.