Association of antibody and T cell receptor repertoires in Trypanosoma cruzi infected rhesus macaques and host response to infection.

Abstract

Background: Chagas disease, caused by Trypanosoma cruzi parasites, leads to chronic cardiac disease in 20-40% of infected patients, while the majority remain asymptomatic. The mechanisms and drivers of pathogenesis are still poorly understood, limiting treatment options. We tested for differences in immunoglobulin (Ig) and T cell receptor (TCR) repertoires and their association with T. cruzi parasite diversity (i.e. the cruziome) and host responses in naturally infected rhesus macaques.

Methods: Ig and TCR complementarity-determination region (CDR)3 sequences were identified from RNA-sequencing data from peripheric blood mononuclear cells of T. cruzi infected rhesus macaques and analyzed for composition and diversity.

Results: T. cruzi chronic infection was associated with a broader Ig clonotype repertoire, while TCR repertoire presented limited clonal expansion. There was a high individual diversity as most of these repertoires were private, although a few public clonotypes were detected. Remarkably, limited differences in Ig and TCR repertoires were found in association with the cruziome of infected macaques, even though parasite diversity seemed to play an important in shaping the immune response.

Conclusion: Chronic T. cruzi infection is associated with strong alterations in Ig and TCR repertoires in rhesus macaques, but these repertoires are minimally affected by parasite diversity and host responses to infection. A better understanding of these processes could help develop new immunotherapies against T. cruzi infection.