Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Li, Lun; Acıoğlu, Çiğdem; Heary, Robert F.; Elkabes, Stella

doi:10.1016/j.bbi.2020.10.007

Cited by 172 publications

(150 citation statements)

References 277 publications

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“…Besides, exposure to the viruses or their components promotes the expression and activation of Toll-like receptors (TLR) in astrocytes. This signaling promotes the production and release of proinflammatory mediators and induces inflammatory responses in the CNS (Figure 2B step 3), eliminating the pathogen as demonstrated for Flavivirus infections (82,120). Therefore, this pathological signaling causes neuronal degeneration and dysfunction of the nerve cells short or long term.…”

Section: Can the Systemic Inflammation By Covid-19 Trigger Neurovascular Disturbance?mentioning

confidence: 93%

Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

et al. 2021

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The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

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Section: Can the Systemic Inflammation By Covid-19 Trigger Neurovascular Disturbance?mentioning

confidence: 93%

Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

et al. 2021

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“…S. aureus triggers TLR2 signaling in astrocytes and the secretion of NO, IL-1β, and TNF-α via NF-kB- and MAPK-dependent pathways ( 156 ). Other studies have shown that TLR activation induces astrocyte chemokine production (CCL2, CCL3, CCL5) and augments adhesion molecule expression ( 157 , 158 ). In astrocytes, the intracellular pattern recognition receptor NOD2 was shown to activate NF-kB leading to IL-6, TNF-α, and co-stimulatory molecule expression, which amplified the anti-bacterial immune response ( 159 ).…”

Section: Other Cell Types In the Brain During S Aureus mentioning

confidence: 98%

Immunopathogenesis of Craniotomy Infection and Niche-Specific Immune Responses to Biofilm

et al. 2021

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Bacterial infections in the central nervous system (CNS) can be life threatening and often impair neurological function. Biofilm infection is a complication following craniotomy, a neurosurgical procedure that involves the removal and replacement of a skull fragment (bone flap) to access the brain for surgical intervention. The incidence of infection following craniotomy ranges from 1% to 3% with approximately half caused by Staphylococcus aureus (S. aureus). These infections present a significant therapeutic challenge due to the antibiotic tolerance of biofilm and unique immune properties of the CNS. Previous studies have revealed a critical role for innate immune responses during S. aureus craniotomy infection. Experiments using knockout mouse models have highlighted the importance of the pattern recognition receptor Toll-like receptor 2 (TLR2) and its adaptor protein MyD88 for preventing S. aureus outgrowth during craniotomy biofilm infection. However, neither molecule affected bacterial burden in a mouse model of S. aureus brain abscess highlighting the distinctions between immune regulation of biofilm vs. planktonic infection in the CNS. Furthermore, the immune responses elicited during S. aureus craniotomy infection are distinct from biofilm infection in the periphery, emphasizing the critical role for niche-specific factors in dictating S. aureus biofilm-leukocyte crosstalk. In this review, we discuss the current knowledge concerning innate immunity to S. aureus craniotomy biofilm infection, compare this to S. aureus biofilm infection in the periphery, and discuss the importance of anatomical location in dictating how biofilm influences inflammatory responses and its impact on bacterial clearance.

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“…Furthermore, astrocytes and microglia have been shown to play an important role in neuroinflammation processes, responding to local inflammation of the CNS and imbalanced peripheral inflammation (Murta et al, 2020). SARS-CoV-2 also is neuro-invasive and can spread to the brain, causing a chronic immune imbalance, which underlies possible long-term effects on synapses and neuropsychiatric disorders (Wu and Tang, 2020;Li et al, 2020). Furthermore, accumulating evidence has shown that neuroglia is the target of several neurotropic viruses that severely affect its function.…”

Section: Possible Mechanism Of Neurological Damagementioning

confidence: 99%

Putative mechanism of neurological damage in COVID-19 infection

Bandala¹,

Cortes-Altamirano²,

Reyes-Long³

et al. 2021

Acta Neurobiologiae Experimentalis

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The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS-CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.

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Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Cited by 172 publications

References 277 publications

Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

Immunopathogenesis of Craniotomy Infection and Niche-Specific Immune Responses to Biofilm

Putative mechanism of neurological damage in COVID-19 infection

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