Effect of inoculation dose on infection kinetics and immune responses to Giardia

Giardia duodenalis is a globally prevalent enteric parasite capable of establishing both acute and chronic infections. While infection dose is known to influence early infection dynamics, its effect on immune activation and chronicity remains poorly defined. In this study, we investigated how varying inoculum sizes affect infection kinetics and immune development in both immunocompetent (C57BL/6J) and T cell-deficient (TKO) mice. High infection doses induced earlier cyst shedding and accelerated interleukin-17A (IL-17A) responses, while lower infection doses resulted in delayed immune activation. Despite these early differences, cumulative cyst excretion and clearance kinetics eventually converged across dose groups. In TKO mice, infection was not controlled regardless of dose, yet parasite loads plateaued, suggesting host-intrinsic limits to expansion. Longitudinal follow-up in C57BL/6J mice revealed persistent low-level infection and sustained upregulation of IL-17A, mannose-binding lectin 2 (Mbl-2) and inducible nitric oxide synthase (NOS2) up to six months post-infection, despite low trophozoite counts. These findings confirm a central role for IL-17A in anti-giardial immunity and suggest that infection dose modulates the timing but not the outcome of immune control. Persistent IL-17A signaling during chronic infection may contribute to long-term host-pathogen interactions, with potential implications for intestinal health and secondary pathogen resistance.