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- PMID: 26459508
- UKPMCID: 26459508
- DOI: 10.1128/IAI.01100-15
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Parasite-specific CD4+IFN-γ+IL-10+ T cells distribute within both lymphoid and non-lymphoid compartments and are controlled systemically by IL-27 and ICOS during blood-stage malaria infection.
Villegas-Mendez, Ana; Shaw, Tovah N; Inkson, Colette A; Strangward, Patrick; de Souza, J Brian; Couper, Kevin N
Infection and immunity. 2015;.
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Full-text held externally
- PMID: 26459508
- UKPMCID: 26459508
- DOI: 10.1128/IAI.01100-15
Abstract
Immune-mediated pathology in IL-10 deficient mice during blood-stage malaria infection typically manifests in non-lymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive non-lymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programmes in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual IFN-γ-YFP and IL-10-GFP reporter mice we show that CD4(+)YFP(+) T cells are the major source of IL-10 in both lymphoid and non-lymphoid compartments throughout the course of blood-stage P. yoelii infection. Mature splenic CD4(+)YFP(+)GFP(+) T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the non-lymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4(+)YFP(+)GFP(+) T cells from the liver and lung produced significantly higher quantities of IL-10 than their splenic counterparts, showing that the CD4(+)YFP(+)GFP(+) T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete non-lymphoid and lymphoid organs, we show that IL-10 production by CD4(+)YFP(+) T cells is controlled systemically during malaria infection through IL-27R signalling that is supported post-CD4(+) T cell priming by ICOS signalling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive non-lymphoid organs.