Circulating Monocytes Exhibit an Endotoxin Tolerance Status after Acute Ischemic Stroke: Mitochondrial DNA as a Putative Explanation for Poststroke Infections
| Autor: | Patricia Martínez-Sánchez, Laura Otero-Ortega, Berta Rodríguez-Frutos, Carolina Cubillos-Zapata, Aníbal Varela-Serrano, Exuperio Díez-Tejedor, Enrique Hernández-Jiménez, José Avendaño-Ortiz, María Gutiérrez-Fernández, María Ángeles Mangas-Guijarro, Alberto Blázquez, Eduardo López-Collazo, Victor Toledano, Blanca Fuentes |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Mitochondrial DNA Immunology Ischemia Biology Infections DNA Mitochondrial Monocytes Immune tolerance 03 medical and health sciences 0302 clinical medicine medicine Immune Tolerance Immunology and Allergy Humans Stroke Cells Cultured Aged Aged 80 and over Innate immune system Blood Cells Antagonist TLR9 Middle Aged medicine.disease Immunity Innate Endotoxins 030104 developmental biology Acute Disease Biomarker (medicine) Female 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 198(5) |
| ISSN: | 1550-6606 |
| Popis: | Patients with acute ischemic stroke (AIS) suffer from infections associated with mortality. The relevance of the innate immune system, and monocytes in particular, has emerged as an important factor in the evolution of these infections. The study enrolled 14 patients with AIS, without previous treatment, and 10 healthy controls. In the present study, we show that monocytes from patients with AIS exhibit a refractory state or endotoxin tolerance. The patients were unable to orchestrate an inflammatory response against LPS and expressed three factors reported to control the evolution of human monocytes into a refractory state: IL-1R–associated kinase-M, NFkB2/p100, and hypoxia-inducible factor-1α. The levels of circulating mitochondrial DNA (mtDNA) in patients with AIS correlated with impaired inflammatory response of isolated monocytes. Interestingly, the patients could be classified into two groups: those who were infected and those who were not, according to circulating mtDNA levels. This finding was validated in an independent cohort of 23 patients with AIS. Additionally, monocytes from healthy controls, cultured in the presence of both sera from patients and mtDNA, reproduced a refractory state after endotoxin challenge. This effect was negated by either a TLR9 antagonist or DNase treatment. The present data further extend our understanding of endotoxin tolerance implications in AIS. A putative role of mtDNA as a new biomarker of stroke-associated infections, and thus a clinical target for preventing poststroke infection, has also been identified. |
| Databáze: | OpenAIRE |
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