From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

Introduction Trypanosoma evansi parasite infections cause a chronic animal wasting disease called Surra, and cases of atypical Human Trypanosomosis (aHT). In experimental models, T. are hallmarked by the early onset excessive inflammation. Therefore, balancing production inflammatory cytokines anti-inflammatory IL-10 is crucial for prolonged survival. Methods To improve understanding trypanosomosis induced immunopathology, we used scRNA-seq data from an infection mouse model, resembling natural in terms characteristics. Results discussion For first time, obtained results allowed to assess transcriptomic profile heterogeneity splenic CD4 + T cell subsets, during trypanosome infection. Here, predominant subpopulation cells was represented Tbx21 (T-bet) Ccr5 Id2 type 1 helper (Th1), followed Icos Cxcr5 Follicular (Tfh) very minor fraction Il2ra (CD25) Foxp3 regulatory (Tregs). Interestingly, Th1 shows that besides Ifng , these express high levels Il10 Il21 coding immunoregulatory cytokines. This coincides with elevated expression key genes involved IL-21 secretion pathway such as Stat1 Stat3 well transcriptional factors Prdm1 (Blimp 1), Maf (c-Maf). contrast, there virtually no transcription detected Treg population. Finally, differential gene ontology analysis infection-induced highlights their suppressive function on activation, differentiation INF-γ itself. indicates infections, cells, rather than Tregs, assume immune role needed dampening