期刊
PLOS PATHOGENS
卷 11, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1004994
关键词
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资金
- Medical Research Council (MRC) [MC UP A253 1028]
- Medical Research Council [MC_U117584248, MC_UP_A253_1028, MC_U117565359] Funding Source: researchfish
- The Francis Crick Institute [10101, 10220] Funding Source: researchfish
- MRC [MC_UP_A253_1028, MC_U117584248, MC_U117565359] Funding Source: UKRI
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 (Il4(gfp)Ifng(yfp)Il17a(FP635)), we demonstrated that Il4(gfp+) Th2 cells purified from in vitro cultures or isolated ex vivo from helminthinfected mice up-regulated IFN. following adoptive transfer into Rag1(-/-) mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFN. 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. 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.
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