Immune Modulation by Plasmodium yoelii: Insights From Lethal and Non-Lethal Strains

Malaria pathogenesis is driven by intricate host-parasite interactions that determine immune balance and clinical outcome. The Plasmodium yoelii model, particularly its lethal (17XL) and non-lethal (17XNL) strains, provides a robust framework to investigate these dynamics. This review integrates recent findings demonstrating that 17XL infections trigger excessive pro-inflammatory cytokine release and immune exhaustion, while 17XNL infections sustain regulated Th1/Th2 responses enabling parasite control and survival. Emerging pathways involving MIF, TLR7 signalling, and immune checkpoints (PD-1, LAG-3) underscore the immunological divergence between strains. Evidence converges on a central concept: malaria severity reflects not parasite load but the timing and resolution of host immune responses. Future research using humanised models, single-cell profiling, and immunomodulatory interventions will deepen our understanding of immune regulation and guide novel therapeutic and vaccine strategies against malaria.