Different pathways involving Tfh cells delay parasite-specific antibody production in Trypanosoma cruzi acute experimental models 9260

Abstract Description Chagas disease (CD) is caused by the parasite Trypanosoma cruzi. 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. 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 parasite-specific IgG2c during early acute infection. 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. Funding Sources This work was funded by the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation (PJH) and R01AI168038 (KMJ). This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (NIAID P30AI036211, NCI P30CA125123, and NCRR S10RR024574) and the assistance of Joel M. Sederstrom. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)