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Article ; Online: STING is ESCRTed to degradation by microautophagy.

Assil, Sonia / Paludan, Søren R

2023 Volume 25, Issue 3, Page(s) 379–380

MeSH term(s)	Microautophagy ; Animals ; Membrane Proteins/metabolism ; Endosomal Sorting Complexes Required for Transport
Chemical Substances	Membrane Proteins ; Endosomal Sorting Complexes Required for Transport
Language	English
Publishing date	2023-03-14
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-022-01084-7
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

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Article ; Online: Microglia and amyloid plaque formation in Alzheimer's disease - Evidence, possible mechanisms, and future challenges.

Fruhwürth, Stefanie / Zetterberg, Henrik / Paludan, Søren R

Journal of neuroimmunology

2024 Volume 390, Page(s) 578342

Abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that severely affects patients and their families. Genetic and environmental risk factors, such as viral infections, synergize to accelerate the aging-associated ... ...

Abstract	Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that severely affects patients and their families. Genetic and environmental risk factors, such as viral infections, synergize to accelerate the aging-associated neurodegeneration. Genetic risk factors for late-onset AD (LOAD), which accounts for most AD cases, are predominantly implicated in microglial and immune cell functions. As such, microglia play a major role in formation of amyloid beta (Aβ) plaques, the major pathological hallmark of AD. This review aims to provide an overview of the current knowledge regarding the role of microglia in Aβ plaque formation, as well as their impact on morphological and functional diversity of Aβ plaques. Based on this discussion, we seek to identify challenges and opportunities in this field with potential therapeutic implications.
Language	English
Publishing date	2024-04-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2024.578342
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Zs.A 1646: Show issues

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Article ; Online: Constitutive and latent immune mechanisms exert 'silent' control of virus infections in the central nervous system.

Paludan, Soren R / Mogensen, Trine H

Current opinion in immunology

2021 Volume 72, Page(s) 158–166

Abstract: Viral infections in the central nervous system (CNS) can lead to severe disease manifestations often mediated by a combination of viral cytopathic effects and immunopathology. Moreover, neuronal tissue and brain activities are highly sensitive to ... ...

Abstract	Viral infections in the central nervous system (CNS) can lead to severe disease manifestations often mediated by a combination of viral cytopathic effects and immunopathology. Moreover, neuronal tissue and brain activities are highly sensitive to excessive inflammation that disturb homeostasis. Immune responses to virus infections in the CNS should therefore be tightly balanced and limited in magnitude and duration to avoid immunopathology and tissue damage. Recent data from genetic studies of patients with viral infections in the CNS as well as experimental cell and animal models have provided evidence of non-redundant roles for constitutive and latent immune mechanisms, which mediate a first line of antiviral control without significantly triggering inflammatory activities. Collectively, accumulating data suggest the existence of a layer of immune mechanisms in the CNS exerting immediate control of infection, hence buffering the need for activation of more potent immune reactions with inherent potential to induce immunopathology and disease.
MeSH term(s)	Alleles ; Animals ; Autophagy ; Biomarkers ; Central Nervous System Infections/immunology ; Central Nervous System Infections/virology ; Disease Susceptibility/immunology ; Genetic Predisposition to Disease ; Genetic Variation ; Host-Pathogen Interactions/immunology ; Humans ; Immunity ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Signal Transduction ; Virus Diseases/immunology ; Virus Diseases/virology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-05-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2021.05.004
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Zs.A 2773: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 13: Show issues

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Article ; Online: Innate immunological pathways in COVID-19 pathogenesis.

Paludan, Søren R / Mogensen, Trine H

Science immunology

2022 Volume 7, Issue 67, Page(s) eabm5505

Abstract: Coronavirus disease 2019 (COVID-19) is a disease characterized by a profound dysregulation of the innate immune system. This knowledge has emerged from the large body of single-cell omics studies of patients with COVID-19, which have provided one of the ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is a disease characterized by a profound dysregulation of the innate immune system. This knowledge has emerged from the large body of single-cell omics studies of patients with COVID-19, which have provided one of the most detailed cellular atlases of a human disease ever. However, we are only beginning to understand the innate immunological pathways that govern host defense and immunopathology in COVID-19. In this review, we discuss the emerging understanding of how SARS-CoV-2 and host-derived molecules activate specific pattern recognition receptors to elicit protective interferon responses and pathological cytokine responses, with particular focus on acute infection of the lung and lung pathophysiology in critical COVID-19. In addition, we discuss how these pathways are modulated by virus-host interactions and host stress-sensing pathways. In-depth understanding of the disease mechanisms will likely uncover specific molecular targets for the treatment of COVID-19 and other emerging viral infections. In addition, it will reveal the fine balance between beneficial protective versus pathological disease causing immune responses.
MeSH term(s)	COVID-19/immunology ; COVID-19/pathology ; COVID-19/physiopathology ; Humans ; Immunity, Innate ; Lung/immunology ; Lung/pathology ; Lung/physiopathology ; SARS-CoV-2/immunology ; Signal Transduction/immunology
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abm5505
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Article ; Online: Innate Antiviral Defenses Independent of Inducible IFNα/β Production.

Paludan, Søren R

Trends in immunology

2016 Volume 37, Issue 9, Page(s) 588–596

Abstract: The type I interferons (IFNs) (IFNα and IFNβ) not only have potent antiviral activities, but also have pathological functions if produced at high levels or over a long time. Recent articles have described antiviral immune mechanisms that are activated in ...

Abstract	The type I interferons (IFNs) (IFNα and IFNβ) not only have potent antiviral activities, but also have pathological functions if produced at high levels or over a long time. Recent articles have described antiviral immune mechanisms that are activated in response to virus infection at epithelial surfaces independently of IFNα and IFNβ. This may allow the host to exert rapid local antiviral activity and only induce a full-blown, and potentially pathological, type I IFN response in situations where stronger protective immunity is needed. Here, I describe the emerging understanding of early antiviral defenses, which are independent of type I IFN responses, and also discuss how this enables tissues to exert rapid antiviral activities and to limit type I IFN production.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Humans ; Immunity, Innate ; Interferon-alpha/immunology ; Interferon-alpha/metabolism ; Interferon-beta/immunology ; Interferon-beta/metabolism ; Mucous Membrane/immunology ; Mucous Membrane/virology ; Virus Diseases/immunology ; Virus Diseases/therapy
Chemical Substances	Antiviral Agents ; Interferon-alpha ; Interferon-beta (77238-31-4)
Language	English
Publishing date	2016-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2016.06.003
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 2: Show issues

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Article ; Online: T. gondii

Nandakumar, Ramya / Paludan, Søren R

The Journal of biological chemistry

2019 Volume 294, Issue 45, Page(s) 16509–16510

Abstract: Toxoplasma ... ...

Abstract	Toxoplasma gondii
MeSH term(s)	Animals ; Antiviral Agents ; Interferons ; Protozoan Proteins ; Toxoplasma
Chemical Substances	Antiviral Agents ; Protozoan Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2019-11-08
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.H119.011296
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Uc I Zs.108: Show issues

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Article ; Online: STING is redundant for host defense and pathology of COVID-19-like disease in mice.

Marino, Giorgia / Zhang, Baocun / Schmitz, Alexander / Schwensen, Hanna Vf / Reinert, Line S / Paludan, Søren R

Life science alliance

2023 Volume 6, Issue 8

Abstract: Critical COVID-19 is characterized by lack of early type I interferon-mediated host defense and subsequent hyper-inflammation in the lungs. Aberrant activation of macrophages and neutrophils has been reported to lead to excessive activation of innate ... ...

Abstract	Critical COVID-19 is characterized by lack of early type I interferon-mediated host defense and subsequent hyper-inflammation in the lungs. Aberrant activation of macrophages and neutrophils has been reported to lead to excessive activation of innate immunological pathways. It has recently been suggested that the DNA-sensing cGAS-STING pathway drives pathology in the SARS-CoV-2-infected lungs, but mechanistic understanding from in vivo models is needed. Here, we tested whether STING is involved in COVID-19-like disease using the K18-hACE2 mouse model. We report that disease development after SARS-CoV-2 infection is unaltered in STING-deficient K18-hACE2 mice. In agreement with this, STING deficiency did not affect control of viral replication or production of interferons and inflammatory cytokines. This was accompanied by comparable profiles of infiltrating immune cells into the lungs of infected mice. These data do not support a role for STING in COVID-19 pathology and calls for further investigation into the pathogenesis of critical COVID-19.
MeSH term(s)	Mice ; Animals ; Immunity, Innate ; Signal Transduction ; COVID-19 ; SARS-CoV-2/metabolism ; Interferon Type I/metabolism
Chemical Substances	K-18 conjugate ; Interferon Type I
Language	English
Publishing date	2023-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202301997
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Activation and regulation of DNA-driven immune responses.

Paludan, Søren R

Microbiology and molecular biology reviews : MMBR

2015 Volume 79, Issue 2, Page(s) 225–241

Abstract: The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the ... ...

Abstract	The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally, several reports have demonstrated how defects in DNA sensing, signaling, and regulation are associated with susceptibility to infections or inflammatory diseases in humans and model organisms. In this review, the current literature on DNA-stimulated innate immune activation is discussed, and important new questions facing this field are proposed.
MeSH term(s)	Animals ; DNA/immunology ; DNA/metabolism ; Humans ; Immune Evasion ; Immunity, Innate/genetics ; Interferon Type I/genetics ; Membrane Proteins/metabolism ; Signal Transduction/genetics ; Viruses/genetics ; Viruses/immunology ; Viruses/metabolism
Chemical Substances	Interferon Type I ; Membrane Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1376131-6
ISSN	1098-5557 ; 1070-6275 ; 1092-2172
ISSN (online)	1098-5557 ; 1070-6275
ISSN	1092-2172
DOI	10.1128/MMBR.00061-14
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Ud II Zs.96: Show issues

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Article ; Online: In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

Wei, Anji / Yin, Di / Zhai, Zimeng / Ling, Sikai / Le, Huangying / Tian, Lijia / Xu, Jianjiang / Paludan, Soren R / Cai, Yujia / Hong, Jiaxu

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 11, Page(s) 3163–3175

Abstract: In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe ... ...

Abstract	In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.
MeSH term(s)	Humans ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; Keratitis, Herpetic/therapy ; Keratitis, Herpetic/drug therapy ; Cornea ; Herpesvirus 1, Human/genetics
Language	English
Publishing date	2023-08-31
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.08.021
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Zs.A 5640: Show issues

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Article ; Online: TREM2 is down-regulated by HSV1 in microglia and involved in antiviral defense in the brain.

Fruhwürth, Stefanie / Reinert, Line S / Öberg, Carl / Sakr, Marcelina / Henricsson, Marcus / Zetterberg, Henrik / Paludan, Søren R

Science advances

2023 Volume 9, Issue 33, Page(s) eadf5808

Abstract: Immunological control of viral infections in the brain exerts immediate protection and also long-term maintenance of brain integrity. Microglia are important for antiviral defense in the brain. Here, we report that herpes simplex virus type 1 (HSV1) ... ...

Abstract	Immunological control of viral infections in the brain exerts immediate protection and also long-term maintenance of brain integrity. Microglia are important for antiviral defense in the brain. Here, we report that herpes simplex virus type 1 (HSV1) infection of human induced pluripotent stem cell (hiPSC)-derived microglia down-regulates expression of genes in the TREM2 pathway. TREM2 was found to be important for virus-induced
MeSH term(s)	Animals ; Humans ; Mice ; Brain ; Herpes Simplex/immunology ; Herpes Simplex/virology ; Herpesvirus 1, Human/physiology ; Induced Pluripotent Stem Cells ; Membrane Glycoproteins/metabolism ; Microglia ; Receptors, Immunologic/metabolism
Chemical Substances	Membrane Glycoproteins ; Receptors, Immunologic ; TREM2 protein, human
Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adf5808
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