Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a

Vavougios, George D.; Mavridis, Theodoros; Artemiadis, Artemios; Krogfelt, Karen A.; Hadjigeorgiou, Georgios M.

doi:10.1016/j.bbadis.2022.166430

Cited by 11 publications

(15 citation statements)

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“…Building upon previous works from Vavougios et al and others, this manuscript outlines a potential opportunity to formulate a working, testable hypothesis on SAND with implications on cognitive impairment and other dementias. Furthermore, as we have previously indicated, we outline targets that are both testable and druggable ( 51 ), and could serve in the design of future clinical and translational studies.…”

Section: Discussionmentioning

confidence: 99%

“…Dysfunctions of IFITMs and OASs on a pathway level not only have the potential to abrogate antiviral activity, but several studies suggest this dysfunction enables these factors to act as pro-viral factors ( 47 – 49 ). Vavougios and colleagues found that IFN-I signatures containing members of these ISG families are common in neurons, peripheral immune cells, and microglia affected by COVID-19 or by AD ( 10 , 15 , 33 , 50 , 51 ).…”

Section: The Viral Lifecycle: Kinase Recruitment and Tauopathymentioning

confidence: 99%

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Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis

2022

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Epidemiological, clinical, and radiological studies have provided insights into the phenomenology and biological basis of cognitive impairment in COVID-19 survivors. Furthermore, its association with biomarkers associated with neuroinflammation and neurodegeneration supports the notion that it is a distinct aspect of LongCOVID syndrome with specific underlying biology. Accounting for the latter, translational studies on SARS-CoV-2's interactions with its hosts have provided evidence on type I interferon dysregulation, which is seen in neuroinflammatory and neurodegenerative diseases. To date, studies attempting to describe this overlap have only described common mechanisms. In this manuscript, we attempt to propose a mechanistic model based on the host-virus interaction hypothesis. We discuss the molecular basis for a SARS-CoV-2-associated neurocognitive disorder (SAND) focusing on specific genes and pathways with potential mechanistic implications, several of which have been predicted by Vavougios and their research group. Furthermore, our hypothesis links translational evidence on interferon-responsive gene perturbations introduced by SARS-CoV-2 and known dysregulated pathways in dementia. Discussion emphasizes the crosstalk between central and peripheral immunity via danger-associated molecular patterns in inducing SAND's emergence in the absence of neuroinfection. Finally, we outline approaches to identifying targets that are both testable and druggable, and could serve in the design of future clinical and translational studies.

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Section: Discussionmentioning

confidence: 99%

Section: The Viral Lifecycle: Kinase Recruitment and Tauopathymentioning

confidence: 99%

Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis

2022

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“…Previous works from our group developed a model for the pathogenesis of CNS injury following COVID-19, and the overlap between the mechanisms that mediated with Alzheimer’s disease ( Vavougios et al, 2021b , 2022a , b , c ). We built this model upon in silico evidence of overlapping immune pathway dysregulation between peripheral blood and central nervous system sites in Alzheimer’s disease patients ( Vavougios et al, 2020 ).…”

Section: Tonic Type I Interferon Signaling Dysregulation As a Shared ...mentioning

confidence: 99%

“…This transmission would require the interface between a peripheral site (e.g., the olfactory neuroepithelium, the brain vascular endothelium; Vavougios et al, 2022c ) and a central site (such as the hippocampus) ( Vavougios et al, 2021b ). While peripheral stimulation persists, central sites would be exposed to prolonged IFN-I signaling and proinflammatory conditions which would be deleterious to neurogenesis, synaptogenesis and by extent, cognition ( Vavougios et al, 2022a , b ; Crook et al, 2023 ). Once IFN-I signaling has been localized to the CNS, it may become feed-forward due to the production of (DAMPs), a concept displayed experimentally in Alzheimer’s disease ( Roy et al, 2020 , 2022 ) with therapeutic implications for targeting both microglial responses and IFN-I ( Moore et al, 2020 ).…”

Section: Tonic Type I Interferon Signaling Dysregulation As a Shared ...mentioning

confidence: 99%

“…Type I interferon signaling has been shown to both directly affect cognition, and modulate long-term neuroinflammatory and neurotoxic effects for Alzheimer’s disease through microgliosis ( Roy et al, 2020 , 2022 ), beta-amyloidosis ( Hur et al, 2020 ) and tauopathy ( Jin et al, 2021 ; Udeochu et al, 2023 ). A growing body of human studies and disease models of Alzheimer’s disease consistently reports on dysregulated type I interferon signaling (See Supplementary Material 1 for an extended presentation of relevant studies) ( Blank and Prinz, 2017 ; Jin et al, 2022 ; Sanford and McEwan, 2022 ; Vavougios et al, 2022b ).…”

Section: Introductionmentioning

confidence: 99%

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Type I interferon signaling, cognition and neurodegeneration following COVID-19: update on a mechanistic pathogenetic model with implications for Alzheimer’s disease

Vavougios,

Tseriotis,

Liampas

et al. 2024

Front. Hum. Neurosci.

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COVID-19’s effects on the human brain reveal a multifactorial impact on cognition and the potential to inflict lasting neuronal damage. Type I interferon signaling, a pathway that represents our defense against pathogens, is primarily affected by COVID-19. Type I interferon signaling, however, is known to mediate cognitive dysfunction upon its dysregulation following synaptopathy, microgliosis and neuronal damage. In previous studies, we proposed a model of outside-in dysregulation of tonic IFN-I signaling in the brain following a COVID-19. This disruption would be mediated by the crosstalk between central and peripheral immunity, and could potentially establish feed-forward IFN-I dysregulation leading to neuroinflammation and potentially, neurodegeneration. We proposed that for the CNS, the second-order mediators would be intrinsic disease-associated molecular patterns (DAMPs) such as proteopathic seeds, without the requirement of neuroinvasion to sustain inflammation. Selective vulnerability of neurogenesis sites to IFN-I dysregulation would then lead to clinical manifestations such as anosmia and cognitive impairment. Since the inception of our model at the beginning of the pandemic, a growing body of studies has provided further evidence for the effects of SARS-CoV-2 infection on the human CNS and cognition. Several preclinical and clinical studies have displayed IFN-I dysregulation and tauopathy in gene expression and neuropathological data in new cases, correspondingly. Furthermore, neurodegeneration identified with a predilection for the extended olfactory network furthermore supports the neuroanatomical concept of our model, and its independence from fulminant neuroinvasion and encephalitis as a cause of CNS damage. In this perspective, we summarize the data on IFN-I as a plausible mechanism of cognitive impairment in this setting, and its potential contribution to Alzheimer’s disease and its interplay with COVID-19.

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Systems biology in COVID-19

Vavougios

Zarogiannis

Gourgoulianis

2023

Omics Approaches and Technologies in COVID-19

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Trained immunity in viral infections, Alzheimer's disease and multiple sclerosis: A convergence in type I interferon signalling and IFNβ-1a

Cited by 11 publications

References 61 publications

Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis

Type I interferon signaling in SARS-CoV-2 associated neurocognitive disorder (SAND): Mapping host-virus interactions to an etiopathogenesis

Type I interferon signaling, cognition and neurodegeneration following COVID-19: update on a mechanistic pathogenetic model with implications for Alzheimer’s disease

Systems biology in COVID-19

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