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

Xiao, Yu; Cai, Baowei; Wang, Mingjun; Tan, Peng; Ding, Xiaoyu; Wu, Jian; Li, Jian; Li, Qingtian; Liu, Pinghua; Xing, Changsheng; Wang, Helen Yicheng; Su, Xin-zhuan; Wang, Rongfu

doi:10.1016/j.immuni.2016.10.001

Cited by 104 publications

(191 citation statements)

References 37 publications

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“…During viral infection, the TLR9-myeloid differentiation primary response 88 (MYd88)-IRF3/7 pathway is necessary for mouse monocytes recruitment to lymph nodes, whereas the STING pathway is necessary for local production of type-I IFN (112). However, STING signaling can induce suppressor of cytokine signaling1 (SOCS1) expression, which can negatively regulate MyD88 activity (113) (Figure 3C).…”

Section: Cross-regulation Of the Cgas-sting Pathway With Other Dna-sementioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immunesurveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.

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Section: Cross-regulation Of the Cgas-sting Pathway With Other Dna-sementioning

confidence: 99%

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

2020

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“…Furthermore, for parasite infections of the liver such as Plasmodium spp. there is important evidence on the importance of the IFN-α signaling (13,(179)(180)(181)(182). Due the regulatory interactions of IFN-α and IFN-λ and the clinical importance of relevant SNPs (31), it is not unreasonable to postulate an impact.…”

Section: Parasite and Fungal Infectionsmentioning

confidence: 99%

Interferon Lambda: Modulating Immunity in Infectious Diseases

2017

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Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

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“…Activation of PRRs has at least two roles in host immunity during blood-stage malaria infection: (a) direct control of parasite replication and/or parasite killing via innate immune effector mechanisms and (b) generation of cues that expand and differentiate antigen-specific CD4 + T cells and B cells (3)(4)(5). It was recently reported that the PRR cyclic GMP-AMP synthase (cGAS) was a critical innate signal in the context of a murine model of lethal malaria (6). We used a nonlethal murine model of blood-stage malaria (Plasmodium yoelii 17XNL) to determine the role that cGAS plays in the generation of the humoral immune response and, specifically, immunologic memory.…”

Section: Introductionmentioning

confidence: 99%

cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses

Hahn¹,

Butler²,

Lindner³

et al. 2018

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

Cited by 104 publications

References 37 publications

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response

Interferon Lambda: Modulating Immunity in Infectious Diseases

cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses

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