The interplay between Trypanosoma cruzi and the microbiome of Triatoma infestans: Implications for the host's immune response

The infection dynamics of Trypanosoma cruzi is shaped by the parasite's genetics and interactions with host and vector factors. While most studies in the area use axenic parasite cultures devoid of insect fecal components, this study is focused on the immune response and the parasite loads generated after the interaction of T. cruzi with feces from Triatoma infestans in a murine model. First, using metagenomics, we analyzed the microbiota of infected and uninfected feces. Illumina sequencing of the 16S rRNA gene (V3-V4 region) revealed a predominance of the genus Arsenophonus in infected feces and of Enterococcus in uninfected ones. C57BL/6J mice inoculated with T. cruzi infected feces, displayed distinct immune responses compared to those inoculated with culture-derived metacyclic trypomastigotes alone, with lower levels of pro-inflammatory cytokines (IFN-ɣ, TNF-α) and higher amounts of IL-10, suggesting a regulatory response. Besides, total anti-T. cruzi IgG levels remained similar among groups, but IgG1 and IgG2c were reduced in the T. cruzi infected feces group, indicating a balanced Th1/Th2 response. Notably, mice inoculated with T. cruzi infected feces demonstrated significantly reduced blood and muscle parasite loads, potentially limiting inflammation and parasite dissemination. These findings highlight the possible role of vector fecal microbiota in shaping immune responses and influencing disease outcomes during natural T. cruzi infections.