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Different responses involving Tfh cells delay parasite-specific antibody production in Trypanosoma cruzi acute
Ana Carolina Leão1,2, Maria Jose Villar1,2, Rakesh Adhikari1,2
1Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, United States.
Insights
Mice infected with Trypanosoma cruzi show different immune responses. BALB/c mice had a strong but unspecific antibody response, while C57BL/6 mice had a weaker, more targeted response, aiding parasite clearance.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- Chagas disease (CD) affects millions globally, with limited treatment options for chronic infections.
- Understanding the immune response to *Trypanosoma cruzi* is vital for developing effective vaccines and therapies.
Purpose of the Study:
- To investigate and compare the T follicular helper (Tfh) and B cell immune responses to *T. cruzi* infection in BALB/c and C57BL/6 mice.
- To elucidate the role of these responses in parasite-specific antibody production during acute infection.
Main Methods:
- Infection of female BALB/c and C57BL/6 mice with *T. cruzi* H1 K68 strain.
- Analysis of splenic Tfh and B cell populations using flow cytometry at 14, 28, and 49 days post-infection.
Main Results:
- BALB/c mice mounted a Th2-biased response with abundant Tfh and GC B cells, leading to polyclonal B cell activation and hypergammaglobulinemia, but poor parasite clearance.
- C57BL/6 mice exhibited a Th1-skewed response with "Th1-like Tfh" cells (IFN-γ+, CXCR5+), associated with reduced parasite burden and a more focused antibody response, including parasite-specific IgG2c.
Conclusions:
- Distinct Tfh cell-mediated immune responses influence B cell activation and antibody production in different mouse models of *T. cruzi* infection.
- The findings suggest that the "Th1-like Tfh" response in C57BL/6 mice may be more effective in controlling parasite burden despite weaker specific antibody production.
- This study offers novel insights into Tfh cell dynamics and antibody production in Chagas disease, identifying potential therapeutic targets.
Introduction:
Chagas disease (CD), caused by the parasite Trypanosoma cruzi, affects millions globally. Despite treatment options in the acute phase, most infections progress to a chronic indeterminate form or develop severe cardiac/gastrointestinal complications. Understanding the immune response is crucial for the development of vaccines and more efficient drugs for the disease control.
Methods:
This work investigates the immune response to T. cruzi H1 K68 strain infection in female BALB/c and C57BL/6 mice to characterize differences in Tfh and B cell responses that may be involved in the poor parasite-specific antibody production during acute infection. For this, mice were euthanized 14, 28, and 49 days after infection, and splenic T and B cell populations were evaluated by flow cytometry.
Results:
BALB/c mice exhibited a strong Th2-biased response with a massive expansion of classic Tfh cells and GC B cells, potentially linked with polyclonal B cell activation and hypergammaglobulinemia, but not with efficient parasite clearance. C57BL/6 mice displayed a Th1-skewed response with a population of "Th1-like Tfh" cells expressing IFN-γ and CXCR5 associated with lower parasite burden and more focused antibody response, including parasitespecific IgG2c during early acute infection.
Discussion:
These findings suggest that these mouse models develop different immune responses mediated by Tfh cells, which are crucial for B cell activation and antibody production. The massive expansion of Tfh cells in BALB/c mice might lead to unspecific antibody production due to excessive B cell activation. Conversely, C57BL/6 mice exhibit a "Th1-like Tfh" response lacking classic Tfh cells, potentially explaining their weak parasite-specific antibody production throughout the acute infection. Overall, this study provides for the first time insights into the complex interplay between Tfh cells and antibody production during T. cruzi infection, suggesting potential targets for therapeutic intervention in CD.
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