IL-27 promotes IL-10 production by effector Th1 CD4 +T cells

A critical mechanism for protection from severe immunopathology during malaria infection

Ana Paula Freitas Do Rosário, Tracey Lamb, Philip Spence, Robin Stephens, Agathe Lang, Axel Roers, Werner Muller, Anne O'Garra, Jean Langhorne

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. The establishment of a precise balance between the pro- and anti-inflammatory responses is critical to guarantee control of the parasite and survival of the host. IL-10, a key regulatory cytokine produced by many cells of the immune system, has been shown to protect mice against pathology during acute Plasmodium chabaudi chabaudi AS model of malaria. However, the critical cellular source of IL-10 is still unknown. In this article, we demonstrate that T cell-derived IL-10 is necessary for the control of pathology during acute malaria, as mice bearing specific deletion of Il10 in T cells fully reproduce the phenotype observed in Il10 -/- mice, with significant weight loss, decline in temperature, and increased mortality. Furthermore, we show that IFN-γ + Th1 cells are the main producers of IL-10 throughout acute infection, expressing high levels of CD44 and ICOS, and low levels of CD127. Although Foxp3 + regulatory CD4 + T cells produce IL-10 during infection, highly activated IFN-γ + Th1 cells were shown to be the essential and sufficient source of IL-10 to guarantee protection against severe immune-mediated pathology. Finally, in this model of malaria, we demonstrate that the generation of protective IL10 +IFN-γ + Th1 cells is dependent on IL-27 signaling and independent of IL-21.

Original languageEnglish (US)
Pages (from-to)1178-1190
Number of pages13
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012

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Interleukin-27
Interleukin-10
Malaria
T-Lymphocytes
Infection
Th1 Cells
Pathology
Plasmodium chabaudi
Plasmodium malariae
Communicable Disease Control
Regulatory T-Lymphocytes
Weight Loss
Immune System
Parasites
Anti-Inflammatory Agents
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

IL-27 promotes IL-10 production by effector Th1 CD4 +T cells : A critical mechanism for protection from severe immunopathology during malaria infection. / Do Rosário, Ana Paula Freitas; Lamb, Tracey; Spence, Philip; Stephens, Robin; Lang, Agathe; Roers, Axel; Muller, Werner; O'Garra, Anne; Langhorne, Jean.

In: Journal of Immunology, Vol. 188, No. 3, 01.02.2012, p. 1178-1190.

Research output: Contribution to journalArticle

Do Rosário, Ana Paula Freitas ; Lamb, Tracey ; Spence, Philip ; Stephens, Robin ; Lang, Agathe ; Roers, Axel ; Muller, Werner ; O'Garra, Anne ; Langhorne, Jean. / IL-27 promotes IL-10 production by effector Th1 CD4 +T cells : A critical mechanism for protection from severe immunopathology during malaria infection. In: Journal of Immunology. 2012 ; Vol. 188, No. 3. pp. 1178-1190.
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