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Background <p>Chagas disease, caused by <i>Trypanosoma cruzi</i> 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 <i>T. cruzi</i> parasite diversity (i.e. the cruziome) and host responses in naturally infected rhesus macaques. </p> Methods <p>Ig and TCR complementarity-determination region (CDR)3 sequences were identified from RNA-sequencing data from peripheric blood mononuclear cells of <i>T. cruzi </i>infected rhesus macaques and analyzed for composition and diversity.</p> Results <p><i>T. cruzi</i> 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.</p> Conclusion <p>Chronic <i>T. cruzi</i> 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 <i>T. cruzi</i> infection.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月18日

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  • Rachel M. Clear,
  • Weihong Tu,
  • Kelly Goff,
  • Preston A. Marx,
  • Claudia Herrera,
  • Eric Dumonteil

摘要

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.