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Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice
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Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice
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Journal Article
Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice
2024
Overview
Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6C
hi
monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1β and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes postacute cognitive deficits. Vaccination with a low dose of adenoviral-vectored spike protein prevents hippocampal production of IL-1β during breakthrough SARS-CoV-2 infection, loss of neurogenesis and subsequent memory deficits. Our study identifies IL-1β as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new mouse model that is prevented by vaccination.
SARS-CoV-2 has been shown to induce IL-1β-mediated neuroinflammation in humans and rodent models. Klein and colleagues show that low-dose COVID-19 vaccination prevents breakthrough infection-mediated hippocampal dysfunction and cognitive memory decline in mouse models.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ COVID-19
/ COVID-19 - prevention & control
/ COVID-19 Vaccines - immunology
/ Female
/ Humans
/ IL-1β
/ Interleukin-1beta - immunology
/ Interleukin-1beta - metabolism
/ Male
/ Memory
/ Memory Disorders - immunology
/ Mice
/ Receptors, Interleukin-1 Type I - genetics
/ Receptors, Interleukin-1 Type I - metabolism
/ Severe acute respiratory syndrome coronavirus 2
