title: Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-malaria Immunity and Host Mortality.
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.
authors: School of Life Sciences, Sun Yat-Sen University, 510275 Guangzhou, P.R. China; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Xiao
authors: X
authors: Yu
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361005 Fujian, P.R. China.
authors: Baowei
authors: B
authors: Cai
authors: Zhongshan School of Medicine, Sun Yat-Sen University, 510275 Guangzhou, P.R. China; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Mingjun
authors: M
authors: Wang
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
authors: Peng
authors: P
authors: Tan
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Xilai
authors: X
authors: Ding
authors: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Jian
authors: J
authors: Wu
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361005 Fujian, P.R. China.
authors: Jian
authors: J
authors: Li
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Qingtian
authors: Q
authors: Li
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Pinghua
authors: P
authors: Liu
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Changsheng
authors: C
authors: Xing
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Helen Y
authors: HY
authors: Wang
authors: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361005 Fujian, P.R. China; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: xsu@niaid.nih.gov.
authors: Xin-Zhuan
authors: XZ
authors: Su
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA. Electronic address: rwang3@houstonmethodist.org.
authors: Rong-Fu
authors: RF
authors: Wang
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D055785:Gene Knockdown Techniques; D007370:Interferon Type I / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010967:Plasmodium yoelii; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D007370:Interferon Type I
keywords: Innate immune response; Malaria infection; Plasmacytoid dendritic cells; Type I IFN signaling