Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 15, 2025

Cerebral endothelial cells (CEC) that form the brain capillaries are principal constituents of blood barrier (BBB), main active interface between and which plays a protective role by restricting infiltration pathogens, harmful substances immune into while allowing entry essential nutrients. Aberrant CEC function often leads to increased permeability BBB altering bidirectional communication bloodstream facilitating extravasation brain. In addition their as gatekeepers BBB, exhibit cell properties they can receive transmit signals partly via release inflammatory effectors in pathological conditions. express innate receptors, including toll like receptors (TLRs) inflammasomes first sensors exogenous or endogenous dangers initiators responses drive neural dysfunction degeneration. Accumulating evidence indicates activation TLRs compromises integrity, promotes aberrant neuroimmune interactions modulates both systemic neuroinflammation, common features neurodegenerative psychiatric diseases central nervous system (CNS) infections injuries. The goal present review is provide an overview pivotal roles played discuss molecular cellular mechanisms contribute disruption neuroinflammation especially context traumatic ischemic injuries infections. We will focus on most recent advances literature reports field highlight knowledge gaps. future research directions advance our understanding contribution potential at promising therapeutic targets wide variety conditions

Язык: Английский

Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes

Open Biology, Год журнала: 2024, Номер 14(6)

Опубликована: Июнь 1, 2024

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different via vascular system. We studied impact of apolipoprotein E (APOE) genotype inflammation on infectivity pseudo-typed severe acute syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse human cultured endothelial cells pericytes. Possessing APOE4 allele or having existing systemic enhance severity COVID-19. Using targeted replacement APOE3 mice induced bacterial lipopolysaccharide (LPS), we investigated infection SARS-CoV-2. Here, show that higher murine cerebrovascular pericytes compared cultures expressing APOE4. Furthermore, increasing inflammatory state prior incubation with LPS increased into cells. Our findings provide insights mechanisms underlying infection, highlighting how risk factors such as may exacerbate augmenting virus’s ability infect

Язык: Английский