In vivo reduction of Treg expansion in rodent helminth–malaria coinfection

Abstract Background Parasitic helminths modulate host immunity to establish chronic infections, often expanding regulatory T cells (Tregs) to suppress inflammation. However, how helminths adjust immunomodulation during coinfection with fast-replicating microparasites remains unclear. Here, we investigated the immune modulation dynamics in a murine model coinfected with the nematode Heligmosomoides polygyrus (Hp) and the protozoan Plasmodium yoelii (Py). Methods We compared Treg expansion in single Hp infected and coinfected mice, assessed Hp excretory–secretory products (HES) for Treg induction in vitro, measured expression of the TGF-β mimic Hp-TGM-1 gene, and conducted experimental evolution over eight generations in single and coinfected hosts. Results Although coinfected mice exhibited reduced Treg expansion in vivo, HES collected from worms in single infected and coinfected hosts induced similar Treg expansion in vitro. Furthermore, Hp-TGM-1 expression was found to be upregulated in worms from coinfected hosts. Experimental evolution revealed no consistent differences between Hp lines (i.e., parasites maintained in single infected or coinfected hosts). Conclusions These results suggest that reduced Treg expansion during coinfection is driven by the host rather than the parasite, which informs our understanding of immune modulation in helminth–malaria coinfections.