IL-10 from CD4+CD25−Foxp3−CD127− Adaptive Regulatory T Cells Modulates Parasite Clearance and Pathology during Malaria Infection

PLoS Pathogens

Eleanor M. Riley¹  Daniel G. Blount²  J. Brian de Souza²  Kevin N. Couper²  Julius C. Hafalla²  Yasmine Belkaid³  Mark S. Wilson³  Masahito Kamanaka⁴  Richard A. Flavell⁴ 

[1] Department of Immunology and Molecular Pathology, University College London Medical School, London, United Kingdom;Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom;Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: Parasitic diseases;    T cells;    Plasmodium yoelii;    Regulatory T cells;    Malaria;    Malarial parasites;    Immune response;    Infectious disease control;   

DOI  :  10.1371/journal.ppat.1000004

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. Failure to develop an effective pro-inflammatory response can lead to unrestricted parasite replication, whilst failure to regulate this response leads to the development of severe immunopathology. IL-10 and TGF-β are known to be important components of the regulatory response, but the cellular source of these cytokines is still unknown. Here we have examined the role of natural and adaptive regulatory T cells in the control of malaria infection and find that classical CD4+CD25hi (and Foxp3+) regulatory T cells do not significantly influence the outcome of infections with the lethal (17XL) strain of Plasmodium yoelii (PyL). In contrast, we find that adaptive IL-10-producing, CD4+ T cells (which are CD25−, Foxp3−, and CD127− and do not produce Th1, Th2, or Th17 associated cytokines) that are generated during both PyL and non-lethal P. yoelii 17X (PyNL) infections are able to down-regulate pro-inflammatory responses and impede parasite clearance. In summary, we have identified a population of induced Foxp3− regulatory (Tr1) T cells, characterised by production of IL-10 and down regulation of IL-7Rα, that modulates the inflammatory response to malaria.

【 授权许可】

CC BY