Leukocyte-Released Mediators in Response to Both Bacterial and Fungal Infections Trigger IFN Pathways, Independent of IL-1 and TNF-α, in Endothelial Cells.

Autor:	Le KTT; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Chu X; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Jaeger M; Department of Internal Medicine and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands., Plantinga JA; Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Matzaraki V; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Withoff S; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Joosten LAB; Department of Internal Medicine and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands., Netea MG; Department of Internal Medicine and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands., Wijmenga C; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Department of Immunology, K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway., Li Y; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Moser J; Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, Netherlands., Kumar V; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Department of Internal Medicine and Radboud Centre for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Oct 25; Vol. 10, pp. 2508. Date of Electronic Publication: 2019 Oct 25 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.02508
Abstrakt:	In sepsis, dysregulated immune responses to infections cause damage to the host. Previous studies have attempted to capture pathogen-induced leukocyte responses. However, the impact of mediators released after pathogen-leukocyte interaction on endothelial cells, and how endothelial cell responses vary depending on the pathogen-type is lacking. Here, we comprehensively characterized the transcriptomic responses of human leukocytes and endothelial cells to Gram negative-bacteria, Gram positive-bacteria, and fungi. We showed that whole pathogen lysates induced strong activation of leukocytes but not endothelial cells. Interestingly, the common response of leukocytes to various pathogens converges on endothelial activation. By exposing endothelial cells to leukocyte-released mediators, we observed a strong activation of endothelial cells at both transcription and protein levels. By adding IL-1RA and TNF-α antibody in leukocyte-released mediators before exposing to endothelial cells, we identified specific roles for IL-1 and TNF-α in driving the most, but not all, endothelial activation. We also showed for the first time, activation of interferon response by endothelial cells in response to leukocyte-released mediators, independently from IL-1 and TNF-α pathways. Our study therefore, not only provides pathogen-dependent transcriptional changes in leukocytes and endothelial cells during infections, but also reveals a role for IFN, together with IL1 and TNFα signaling, in mediating leukocyte-endothelial interaction in infections. (Copyright © 2019 Le, Chu, Jaeger, Plantinga, Matzaraki, Withoff, Joosten, Netea, Wijmenga, Li, Moser and Kumar.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu