TLR ligands can activate dendritic cells to provide a MyD88-dependent negative signal for Th2 cell development

Jie Sun, Matthew Walsh, Alejandro V. Villarino, Laura Cervi, Christopher A. Hunter, Yongwon Choi, Edward J. Pearce

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

During infection, CD4+ Th cell responses polarize to become primarily Th1 or Th2. Th1 cells, which make IFN-γ, are crucial for immunity to many bacterial and protozoal infections, whereas Th2 cells, which make IL-4, IL-5, and IL-13, are important for resistance to helminth infections. Polarized Th1 responses are induced by dendritic cells (DCs), which respond to pathogen-derived TLR ligands to produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth, and coordinately process and present Ag in the context of MHC class II to activate naive Th cells. In this study we show that in addition to providing positive signals for Th1 cell development, mouse DCs activated by TLR engagement can also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal, which is not IL-12, IL-18, IL-23, IL-27, or IFN-γ and is not provided via Th1 cells, is dependent upon a MyD88-dependent, TNF receptor-associated factor-6-independent signaling pathway in DCs. The signal is released from DCs in response to activation via TLR ligands and exerts an effect directly on Th cells rather than through a third-party cell. Our findings indicate that DCs can provide potent negative as well as positive instruction for Th response polarization, and that these instructional signals are distinct and independent.

Original languageEnglish (US)
Pages (from-to)742-751
Number of pages10
JournalJournal of Immunology
Volume174
Issue number2
DOIs
StatePublished - Jan 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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