IFN[gamma] and IL-12 Restrict Th2 Responses during Helminth/ Plasmodium Co-Infection and Promote IFN[gamma] from Th2 Cells e1004994

• Published in: PLoS pathogens Vol. 11; no. 7
• Main Authors: Coomes, Stephanie M, Pelly, Victoria S, Kannan, Yashaswini, Okoye, Isobel S, Czieso, Stephanie, Entwistle, Lewis J, Perez-Lloret, Jimena, Nikolov, Nikolay, Potocnik, Alexandre J, Biró, Judit, Langhorne, Jean, Wilson, Mark S
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.07.2015
• Subjects: Cell division; Cytokines; Experiments; Genotype & phenotype; Infections; Malaria; Medical research; Studies; T cell receptors; Tropical diseases
• ISSN: 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004994

Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFN[gamma] or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFN[gamma] following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFN[gamma] were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFN[gamma], but not type I IFN, was required for optimal IFN[gamma] production by Th2 cells. Finally, blockade of IL-12 and IFN[gamma] during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFN[gamma] during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFN[gamma]-secreting cells.