Early Th2 cytokine production in Heligmosomoides polygyrus and Toxoplasma gondii co-infected mice is associated with reduced IFNγ production, increased parasite loads and increased mortality

Abstract

ABSTRACTCo-infections are a common reality but understanding how the immune system responds in this context is complex and can be unpredictable. Despite this, it is key to develop models that will provide better translatability to real world situations. Heligmosomoides polygyrus (parasitic roundworm) and Toxoplasma gondii (protozoan parasite) are well studied organisms that stimulate a characteristic Th2 and Th1 response respectively. IFNγ-producing T cells, NK and γδ T cells contribute to early protective immunity during T. gondii infection. To minimise immunopathology, IL-10 is also key to a successful response. Previous research has found H. polygyrus to improve survival during co-infection with both parasites. IFNγ-producing CD4+ and CD8+ T cells were implicated in this protection. Using a similar approach, we have found the opposite. Our co-infected animals displayed greater mortality and intestinal pathology than either single infection. This was associated with an early increase in Th2 cytokines in the Peyer’s patches, mesenteric lymph nodes and spleen. Co-infected animals also had reduced IFNγ−producing cells at day 5 post T. gondii infection in the Peyer’s patches (CD8 T cells only) and in the MLN (NK, NKT, γδ T, CD4+ T and CD8+ T cells). This correlated with increased parasite loads in the MLN at 10 days post T. gondii infection. Our results demonstrate that co-infection dynamics can vary dramatically and that careful consideration needs to be taken when interpreting data in each situation.