Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality

Xiao Yu, Baowei Cai, Mingjun Wang, Peng Tan, Xilai Ding, Jian Wu, Jian Li, Qingtian Li, Pinghua Liu, Changsheng Xing, Helen Y. Wang, Xin zhuan Su, Rong Fu Wang

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted. Further, we identified SOCS1 as a key negative regulator to inhibit MyD88-dependent type I IFN signaling in pDCs. Finally, we have demonstrated that pDCs, cDCs, and macrophages were required for generating IFN-α/β-induced subsequent protective immunity. Thus, our findings have identified a critical regulatory mechanism of type I IFN signaling in pDCs and stage-specific function of immune cells in generating potent immunity against lethal YM infection.

Original languageEnglish (US)
Pages (from-to)1093-1107
Number of pages15
JournalImmunity
Volume45
Issue number5
DOIs
StatePublished - Nov 15 2016

Keywords

  • Innate immune response
  • Malaria infection
  • Plasmacytoid dendritic cells
  • Type I IFN signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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