Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response

Abstract

Nematode infections, in particular gastrointestinal nematodes, are widespread and co-infections with other parasites and pathogens are frequently encountered in humans and animals. To decipher the immunological effects of a widespread protozoan infection on the anti-helminth immune response we studied a co-infection with the enteric nematode <i>Heligmosomoides polygyrus</i> in mice previously infected with <i>Toxoplasma gondii</i>. Protective immune responses against nematodes are dependent on parasite-specific Th2 responses associated with IL-4, IL-5, IL-13, IgE, and IgG1 antibodies. In contrast, <i>Toxoplasma gondii</i> infection elicits a strong and protective Th1 immune response characterized by IFN-γ, IL-12, and IgG2a antibodies. Co-infected animals displayed significantly higher worm fecundity although worm burden remained unchanged. In line with this, the Th2 response to <i>H. polygyrus</i> in co-infected animals showed a profound reduction of IL-4, IL-5, IL-13, and GATA-3 expressing T cells. Co-infection also resulted in the lack of eosinophilia and reduced expression of the Th2 effector molecule RELM-β in intestinal tissue. In contrast, the Th1 response to the protozoan parasite was not diminished and parasitemia of <i>T. gondii</i> was unaffected by concurrent helminth infection. Importantly, <i>H. polygyrus</i> specific restimulation of splenocytes revealed <i>H. polygyrus</i>-reactive CD4⁺ T cells that produce a significant amount of IFN-γ in co-infected animals. This was not observed in animals infected with the nematode alone. Increased levels of <i>H. polygyrus</i>-specific IgG2a antibodies in co-infected mice mirrored this finding. This study suggests that polarization rather than priming of naive CD4⁺ T cells is disturbed in mice previously infected with <i>T. gondii</i>. In conclusion, a previous <i>T. gondii</i> infection limits a helminth-specific Th2 immune response while promoting a shift toward a Th1-type immune response.