Project description:CD14+ monocytes, the predominant population in human blood, are primarily engaged in host defense and pro-inflammatory cytokine responses. Aberrant monocyte activity causes life-threatening cytokine storms, while dysfunctional monocytes lead to 'immunoparalysis.' Understanding the mechanisms controlling monocyte functions is therefore paramount. Here, we reveal platelets' vital role in human monocytes' pro-inflammatory responses. Natural low platelet counts in patients with immune thrombocytopenia (ITP) , platelet depletion in healthy human monocytes, or in vivo platelet depletion in mice, result in monocyte immunoparalysis, characterized by reduced pro-inflammatory gene expression and weakened cytokine responses to immune challenge. Remarkably, supplementation with fresh platelets reverses monocyte immunoparalysis. In mice, thrombocytopenia results in down-regulation of myeloid innate immune genes, and compromised host defense transcriptional programs in monocytes despite normal responses to LPS. Platelets control monocyte cytokines independently of traditional cross-talk pathways, acting as reservoirs of transcription factors like NF?B and MAPK p38. We pinpointed a vesicle-derived NF?B2 transfer to human monocytes by mass spectrometry-based proteomics. Functionally, platelets proportionally restored impaired cytokine secretion in human monocytes lacking MAPK p38a and NF?B p65 and NF?B2. We unveil the intercellular transfer of inflammatory regulators, positioning platelets as central checkpoints in monocyte-mediated inflammation.
Project description:We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions.
Project description:Platelets are blood cells who play critical roles in numerous biological and disease processes. This study was designed to identify lncRNAs that may play a role in platelet reactivity. In this study, by using large-scale deep sequencing, we determined the expression profiles of lncRNAs in both hyperreactive and hyporeactive human platelets. To determine the potential link between the expression of lncRNAs and the function of platelets, the expression profiles of hyperreactive and hyporeactive platelets were compared. Compared with hyperreactive platelets, deep sequencing analysis demonstrated that differential lncRNA expression was a remarkable characteristic in hyporeactive platelets.
Project description:Human platelets collected from healthy donors according to standard international protocols were pooled and stored at 4ºC during 7 days. The small RNA population changes across the days were evaluated by NGS aproach.
Project description:Human platelets collected from healthy donors according to standard international protocols were pooled and stored at 4ºC during 7 days. The small RNA population changes across the days were evaluated by NGS aproach. The smallRNA population was evaluated at fresh platelets and after 1 day, 2 days, 3 days, 4 days, 5 days and 7 days of storage at 4ºC.
Project description:Differentially expressed genes in Aspergillus fumigatus following exposure to human platelets in a timeseries experiment (15min, 30min, 1h, 3h) compared to untreated fungi as reference using customized Geniom (R) Biochips (febit) comprising 9500 genes (14051 features) were studied in order to gain a better understanding of the way platelets may affect Aspergillus spp. and contribute to antifungal host defense.