Concurrent infection with Heligmosomoides polygyrus suppresses anti‐Plasmodium yoelii protection partially by induction of CD4⁺CD25⁺Foxp3⁺ Treg in mice

Abstract

Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. Co-infection with Hp led to reduced Py-responsive proliferation and IFN-c production of spleen cells, and higher activation of CD4 1 CD25 1 Foxp3 1 Treg. In vivo depletion of Treg recovered anti-Py immunity and rescued co-infected mice from exacerbated malaria. However, we did not observe any obvious ex vivo activation of Treg by either Hp products or living worms. Our results suggest that intestinal nematodes moderate host immune responses during acute malaria infection by aggressive activation of Treg. Elucidation of the mechanisms of Treg activation in situ is a target for future analyses.

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

“…Interestingly, the suppression of immune responses to unrelated Ags that is often observed upon helminth infection was also shown to be associated with Tregs in some studies. Using models of adoptive transfer or depletion by anti-CD25 mAb, Tregs have been identified as one of the helminth-induced cell populations responsible for silencing the pathology in OVA-induced asthma (58)(59)(60)(61) or counteracting the protective immune response to Plasmodium yoelii in a coinfection model (62).…”

Helminth Parasites Alter Protection againstPlasmodiumInfection

“…This susceptibility was associated with a reduced response against Py NXL (i.e., low levels of IFN- γ ) in the spleen cells. As a consequence, it increased the activation of Treg cells [147]. However, the same coinfection at 3 weeks in BALB/c mice decreased the pathology associated with low levels of IFN- γ and increased levels of IL-4, but not IL-10 [148].…”

Schistosome: Its Benefit and Harm in Patients Suffering from Concomitant Diseases

“…They also observed the upregulation of iNOS gene expression in spleen from mice with mixed infections, suggesting an increase of splenic nitric oxide production to have contributed to the protection from P. chabaudi. Although the mechanism of the exacerbation of rodent malaria by schistosome is yet to be sufficiently analyzed, Treg cells have been shown to play an important role in the exacerbation of P. yoelii infection by preceding H. polygyrus infection [61]. Likewise, the induction/expansion of Treg cells by schistosome might be involved in the increased susceptibility to rodent malaria.…”