Immune Functions of Astrocytes in Viral Neuroinfections

Jorgačevski, Jernej; Potokar, Maja

doi:10.3390/ijms24043514

Cited by 16 publications

(9 citation statements)

References 171 publications

(262 reference statements)

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“…This is particularly relevant as brain myeloid cells, including macrophages and microglia, are known to play critical roles in the development and progression of AD [ 21 ]. The identification of GO:0048143 for astrocyte activation, highlighted in red text, implicates not only the important role astrocytes play in the CNS innate immune response to SARS-CoV-2 infection but also their potential role as a viral reservoir in nLongC [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Blood Markers Show Neural Consequences of LongCOVID-19

Tang,

Kido,

Shi

et al. 2024

Cells

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological markers of LongC, we investigated the soluble biomolecules present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected between 2020 and 2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1β was significantly increased in both nLongC and Cov and IL-8 was elevated in only nLongC. Both brain-derived neurotrophic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

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Section: Resultsmentioning

confidence: 99%

Blood Markers Show Neural Consequences of LongCOVID-19

Tang,

Kido,

Shi

et al. 2024

Cells

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“…4 , arrows). Astrocytes are thought to represent a viral reservoir in the brain [ 47 ], which is supported by images showing infection in the brain of the long-term DS COVID survivor (Fig. 1 ) .…”

Section: Discussionmentioning

confidence: 89%

Neuropathological findings in Down syndrome, Alzheimer’s disease and control patients with and without SARS-COV-2: preliminary findings

Granholm,

Englund,

Gilmore

et al. 2024

Acta Neuropathol

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The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer’s disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

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“…First, this study primarily focused on elucidating the protective role of UA against viral mimetic-induced microglial dysfunction, as these cells play an important role in neuroinflammation and subsequent neuronal injury as resident innate immune cells of the CNS. However, recent data suggest that viruses and other immune stimuli can also activate astrocytes ( Hosseini and Korte, 2023 ; Jorgačevski and Potokar, 2023 ). Thus, astrogliosis could also play an important role in neuroinflammation, which should be considered in future studies on therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

The effects of urolithin A on poly I:C-induced microglial activation

Mingo,

Gabele,

Lonnemann

et al. 2024

Front. Cell. Neurosci.

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Neuroinflammation can be triggered by various stimuli, including viral infections. Viruses can directly invade the brain and infect neuronal cells or indirectly trigger a “cytokine storm” in the periphery that eventually leads to microglial activation in the brain. While this initial activation of microglial cells is important for viral clearance, chronic activation leads to excessive inflammation and oxidative stress, which can be neurotoxic. Remarkebly, recent studies have shown that certain viruses such as influenza A virus, coronavirus, herpes virus and Epstein–Barr virus may be involved in the development of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. Therefore, it is important to find therapeutic strategies against chronic neuroinflammation triggered by viral infections. Here, we investigated the effects of urolithin A (UA) on microglial activation in vitro induced by a viral mimetic, poly I:C, in a triple co-culture system of neurons, astrocytes and microglial cells. Immunocytochemistry was used to perform a comprehensive single-cell analysis of the morphological changes of microglia as an indicator of their reactive state. Treatment with UA significantly prevented the poly I:C-induced reactive state of microglia, which was characterized by increased expression of the microglial activation markers CD68 and IBA-1. UA restored the poly I:C-induced morphology by restoring microglial ramification. In addition, UA was able to reduce the release of the pro-inflammatory mediators CCL2, TNF-α, and IL-1β and showed a trend toward attenuation of cellular ROS production in poly I:C-treated cultures. Overall, this study suggests that UA as a component of a healthy diet may help prevent virus-induced neuroinflammation and may have therapeutic potential for future studies to prevent or treat neurodegenerative diseases by targeting the associated neuroinflammatory processes.

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Immune Functions of Astrocytes in Viral Neuroinfections

Cited by 16 publications

References 171 publications

Blood Markers Show Neural Consequences of LongCOVID-19

Blood Markers Show Neural Consequences of LongCOVID-19

Neuropathological findings in Down syndrome, Alzheimer’s disease and control patients with and without SARS-COV-2: preliminary findings

The effects of urolithin A on poly I:C-induced microglial activation

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