Age-dependent dysregulation of innate immunity

Shaw, Albert C.; Goldstein, Daniel R.; Montgomery, Ruth R.

doi:10.1038/nri3547

Cited by 912 publications

(869 citation statements)

References 192 publications

(177 reference statements)

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“…Such conditions might mimic the settings of neonates 16 , elderly 17 , and immunosuppressed individuals, where innate resistance is suboptimal resulting in overdrive of compensatory immune effector mechanisms. Consistent with previous work 11,15 , our findings indicate an antiviral role for CD8 T cells in the ZIKV infection.…”

mentioning

confidence: 99%

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

et al. 2017

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Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly1 and Guillain-Barré syndrome 2,3 as ZIKV-associated neurological complications. Recent reports have further indicated other neurological manifestations to be associated with ZIKV including myelitis 4, meningoencephalitis 5 and fatal encephalitis6. Here, we investigate the neuropathogenesis of ZIKV infection in IFNAR knockout (Ifnar1−/−) mice, an infection model that exhibits high viral burden within the central nervous system (CNS). We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1-deficiency in the hematopoietic compartment. However, spread of ZIKV within the CNS is supported by Ifnar1-deficient non-hematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood-brain barrier and a large influx of CD8+ effector T cells. Further, we find antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but as a consequence instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV-neuropathogenesis within a susceptible mouse model and suggests BBB breakdown and T cell mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

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confidence: 99%

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

et al. 2017

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“…Intrinsic and extrinsic factors responsible for such systemic chronic inflammation, including alterations in chronic viral infections, sex steroids, and debris from other senescent cells, are discussed in two recent reviews (Franceschi, Garagnani, Vitale, Capri, & Salvioli, 2017; Shaw, Goldstein, & Montgomery, 2013). …”

Section: Systems Level Events In Aging and Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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“…Ageing also affects innate and adaptive immune systems (Shaw et al 2013). Furthermore, it has been shown that caloric restriction in old animals reduces the levels of pro-inflammatory cytokines to levels comparable to those of young animals (Spaulding et al 1997).…”

Section: Inflammation and Ageing Inflammagingmentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

343

203

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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Age-dependent dysregulation of innate immunity

Cited by 912 publications

References 192 publications

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Obesity and related consequences to ageing

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