Astrocytes\' Role in the Immune Response to Viral Neuropathies

Elena Koščálová^*
*Correspondence: Elena Koščálová, Department of Infectology and Geographical Medicine, Comenius University, Bratislava, Slovakia, Email:

Keywords

Astrocytes • Immune response • Viral neuropathies • Central nervous system

Introduction

Astrocytes are the most abundant glial cells in the CNS and are integral to maintaining the homeostatic environment required for optimal neuronal function. Historically viewed primarily as supportive cells, their role in the CNS's immune response has garnered significant attention in recent years. Viral neuropathies, which include infections like Herpes Simplex Virus (HSV), Human Immunodeficiency Virus (HIV), and arboviruses such as Zika virus, challenge the CNS's protective mechanisms due to their ability to bypass or disrupt the BBB. The resultant neuroinflammation can lead to severe, often irreversible, neurological damage [1].

Astrocytes are pivotal in the brain's defense against these viral invasions. They participate actively in the immune response by detecting pathogens, secreting cytokines, and interacting with other glial cells and neurons. This review aims to dissect the multifaceted roles of astrocytes in the immune response to viral infections within the CNS, highlighting their importance in both the immediate defense and long-term outcomes of viral neuropathies. Understanding these roles could pave the way for new therapeutic strategies targeting astrocytes to ameliorate or prevent the devastating effects of these infections [2].

Literature Review

Astrocytes, named for their star-shaped morphology, perform various functions crucial to the CNS's integrity. They regulate ion balance, neurotransmitter uptake and recycling, and provide metabolic support to neurons. Additionally, astrocytes are key components of the BBB, a selective permeability barrier that protects the brain from potentially harmful substances while allowing essential nutrients to pass through. One of astrocytes' primary roles is the maintenance of the BBB. This barrier is crucial in preventing pathogens, including viruses, from entering the CNS. Astrocytes contribute to the formation and maintenance of tight junctions between endothelial cells, a critical feature of the BBB. During viral infections, the integrity of the BBB can be compromised, allowing viruses to infiltrate the brain parenchyma. Astrocytes respond to this breach by producing molecules that can either strengthen the BBB or signal for its repair post-invasion [3].

Astrocytes are increasingly recognized as active participants in the CNS's immune responses. They express Pattern Recognition Receptors (PRRs) such as Toll-Like Receptors (TLRs), which detect viral components and trigger innate immune responses. Upon activation, astrocytes can produce a range of cytokines and chemokines, such as interleukin-1β (IL-1β), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ). These molecules recruit and activate various immune cells, including microglia, the resident macrophages of the CNS. The interaction between astrocytes and microglia is critical in the context of CNS viral infections. While microglia are the primary immune cells within the brain, astrocytes modulate microglial activity through the release of cytokines and chemokines [4].

Discussion

Astrocytes' roles in the immune response to viral neuropathies are complex and multifaceted. Their ability to detect viral infections through PRRs and their subsequent production of cytokines and chemokines place them at the forefront of the CNS's defense mechanisms. By regulating the activity of other glial cells and maintaining BBB integrity, astrocytes help to limit viral spread and protect neuronal function. However, this protective role can also have detrimental effects, as the inflammation and immune responses they mediate can lead to neuronal damage and chronic neuroinflammation. Astrocytes detect viral infections primarily through PRRs like TLRs, RIG-I-Like Receptors (RLRs), and Nucleotide-Binding Oligomerization Domain-Like Receptors (NLRs). Upon recognizing viral components such as double-stranded RNA (a common viral replication intermediate), these receptors initiate signaling cascades that lead to the production of antiviral cytokines. For instance, TLR3 recognition of viral RNA results in the activation of NF-κB and IRF3, transcription factors that drive the expression of type I interferons and other pro-inflammatory cytokines [5].

The crosstalk between astrocytes and microglia is a critical aspect of the CNS's immune response to viral infections. Microglia, upon activation by astrocyte-derived cytokines, can produce their own set of inflammatory mediators that further influence astrocyte function. This bidirectional communication ensures a coordinated response to infection but also raises the potential for a vicious cycle of inflammation if not properly regulated. For example, during HSV infection, astrocytes produce IL-6, which enhances microglial antiviral activity. Conversely, microglia can release TNF-α and IL-1β, which amplify astrocytic responses, leading to increased cytokine production and potentially chronic inflammation if the infection is not cleared promptly [6].

Conclusion

Astrocytes play a crucial role in the immune response to viral neuropathies, acting as sentinels that detect viral infections, producing cytokines and chemokines that orchestrate the immune response, and interacting with other glial cells to regulate neuroinflammation. While their actions are essential for controlling infections, they also have the potential to contribute to chronic inflammation and neuronal damage. Understanding the delicate balance of astrocyte functions in the CNS's immune response is critical for developing therapeutic strategies aimed at mitigating the detrimental effects of viral neuropathies while preserving the protective roles of these versatile glial cells. Future research should focus on elucidating the specific signaling pathways and molecular mechanisms involved in astrocyte-mediated immune responses, with the goal of identifying novel targets for therapeutic intervention in viral neuropathies.

Acknowledgement

None.

Conflict of Interest

None.

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