IFNγ and IL-12 Restrict Th2 Responses during Helminth/Plasmodium Co-Infection and Promote IFNγ from Th2 Cells

PLoS Pathogens

Stephanie Czieso¹  Mark S. Wilson¹  Lewis J. Entwistle¹  Alexandre J. Potocnik¹  Stephanie M. Coomes¹  Yashaswini Kannan¹  Isobel S. Okoye¹  Victoria S. Pelly¹  Jimena Perez-Lloret¹  Judit Biró¹  Jean Langhorne²  Nikolay Nikolov³ 

[1] Division of Molecular Immunology, The Francis Crick Institute, London, United Kingdom;Division of Parasitology, Mill Hill Laboratories, London, United Kingdom;Division of Systems Biology, The Francis Crick Institute, London, United Kingdom

关键词: T helper cells;    Co-infections;    Plasmodium;    T cells;    Cytokines;    Helminth infections;    Parasitemia;    Cell-mediated immunity;   

DOI  :  10.1371/journal.ppat.1004994

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 IFNγ 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 IFNγ following adoptive transfer into Rag1–/– mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFNγ were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNγ, but not type I IFN, was required for optimal IFNγ production by Th2 cells. Finally, blockade of IL-12 and IFNγ 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 IFNγ 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 IFNγ-secreting cells.

【 授权许可】

CC BY