| Autor: |
Allison K. Maher, Katie L. Burnham, Emma Jones, Laury Baillon, Claudia Selck, Nicolas Giang, Rafael Argüello, Charlotte-Eve Short, Rachael Quinlan, Wendy S. Barclay, Nichola Cooper, Graham P. Taylor, Emma E. Davenport, Margarita Dominguez-Villar |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.04.03.486830 |
| Popis: |
Alterations in the myeloid immune compartment have been observed in COVID-19, but the specific mechanisms underlying these impairments are not completely understood. Here we examined the functionality of classical CD14+monocytes as a main myeloid cell component in well-defined cohorts of patients with mild and moderate COVID-19 during the acute phase of infection and compared them to that of healthy individuals. We found thatex vivoisolated CD14+monocytes from mild and moderate COVID-19 patients display specific patterns of costimulatory and inhibitory receptors that clearly distinguish them from healthy monocytes, as well as altered expression of histone marks and a dysfunctional metabolic profile. Decreased NFκB activation in COVID-19 monocytesex vivois accompanied by an intact type I IFN antiviral response. Subsequent pathogen sensingex vivoled to a state of functional unresponsiveness characterized by a defect in pro-inflammatory cytokine expression, NFκB-driven cytokine responses and defective type I IFN response in moderate COVID-19 monocytes. Transcriptionally, COVID-19 monocytes switched their gene expression signature from canonical innate immune functions to a pro-thrombotic phenotype characterized by increased expression of pathways involved in hemostasis and immunothrombosis. In response to SARS-CoV-2 or other viral or bacterial components, monocytes displayed defects in the epigenetic remodelling and metabolic reprogramming that usually occurs upon pathogen sensing in innate immune cells. These results provide a potential mechanism by which innate immune dysfunction in COVID-19 may contribute to disease pathology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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