1 research outputs found
Toxoplasma co-infection prevents Th2 differentiation and leads to a helminth- specific Th1 response
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 Heligmosomoides polygyrus in mice
previously infected with Toxoplasma gondii. 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, Toxoplasma
gondii 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 H. polygyrus 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 T. gondii was unaffected by concurrent helminth infection.
Importantly, H. polygyrus specific restimulation of splenocytes revealed H.
polygyrus-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 H. polygyrus-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 T. gondii. In conclusion, a previous T. gondii infection limits
a helminth-specific Th2 immune response while promoting a shift toward a
Th1-type immune response