Purinergic signaling in infectious diseases of the central nervous system

•Purinergic signaling is involved in the pathogenesis of neuroinfectious disease.•P2 receptors have pro-inflammatory and deleterious effects in viral Neuroinfections.•ATP-P2X7 receptor signaling contributes to sepsis-associated encephalopathy.•Adenosine favors brain parasite persistence in cerebral...

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Published in:Brain, behavior, and immunity behavior, and immunity, 2020-10, Vol.89, p.480-490
Main Authors: Alves, Vinícius Santos, Leite-Aguiar, Raíssa, Silva, Joyce Pereira da, Coutinho-Silva, Robson, Savio, Luiz Eduardo Baggio
Format: Article
Language:English
Subjects:
Adenosine
AIDS Dementia Complex - metabolism
Betacoronavirus
CD39
CD73
Central Nervous System Infections - metabolism
Cerebral toxoplasmosis, Zika, SARS-CoV-2
Coronavirus Infections - metabolism
COVID-19
Encephalitis, Herpes Simplex - metabolism
Humans
Malaria - metabolism
Meningitis, Bacterial - metabolism
Meningitis, Cryptococcal - metabolism
Neuroinfections
Neuroinflammation
P2 receptor
Pandemics
Pneumonia, Viral - metabolism
Receptors, Purinergic P1 - metabolism
Receptors, Purinergic P2X - metabolism
Receptors, Purinergic P2Y - metabolism
SARS-CoV-2
Sepsis - metabolism
Signal Transduction
Toxoplasmosis, Cerebral - metabolism
Zika Virus Infection - metabolism
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Summary:•Purinergic signaling is involved in the pathogenesis of neuroinfectious disease.•P2 receptors have pro-inflammatory and deleterious effects in viral Neuroinfections.•ATP-P2X7 receptor signaling contributes to sepsis-associated encephalopathy.•Adenosine favors brain parasite persistence in cerebral toxoplasmosis. The incidence of infectious diseases affecting the central nervous system (CNS) has been increasing over the last several years. Among the reasons for the expansion of these diseases and the appearance of new neuropathogens are globalization, global warming, and the increased proximity between humans and wild animals due to human activities such as deforestation. Neurotropism affecting normal brain function is shared by organisms such as viruses, bacteria, fungi, and parasites. Neuroinfections caused by these agents activate immune responses, inducing neuroinflammation, excitotoxicity, and neurodegeneration. Purinergic signaling is an evolutionarily conserved signaling pathway associated with these neuropathologies. During neuroinfections, host cells release ATP as an extracellular danger signal with pro-inflammatory activities. ATP is metabolized to its derivatives by ectonucleotidases such as CD39 and CD73; ATP and its metabolites modulate neuronal and immune mechanisms through P1 and P2 purinergic receptors that are involved in pathophysiological mechanisms of neuroinfections. In this review we discuss the beneficial or deleterious effects of various components of the purinergic signaling pathway in infectious diseases that affect the CNS, including human immunodeficiency virus (HIV-1) infection, herpes simplex virus type 1 (HSV-1) infection, bacterial meningitis, sepsis, cryptococcosis, toxoplasmosis, and malaria. We also provide a description of this signaling pathway in emerging viral infections with neurological implications such as Zika and SARS-CoV-2.
ISSN:0889-1591
1090-2139
1090-2139
DOI:10.1016/j.bbi.2020.07.026