Proteomics

Dataset Information

0

Human sepsis with plasma samples


ABSTRACT: The project examines the mechanisms of neutrophil dysfunction during sepsis. Our work uncovered the central role of cell free circulating histones in eliminating mature neutrophil in favour of immature cells and characterized the mechanisms that regulate their release following systemic infection. Mature and immature neutrophil Ly6Ghigh and Ly6Glow populations isolated from the spleens of WT and TCRα-deficient mice either naïve or infected with C. albicans were characterized. In addition, these populations were compared to neutrophils isolated from WT mice receiving Clodronate-liposomes and recombinant G-CSF. These studies demonstrated that T-cell derived histones drive the release of G-CSF in the spleen and progressively eliminate mature neutrophils by shortening their lifespan. Finally, we conducted proteomic analysis of plasmas isolated from patients with microbial sepsis to correlate markers of neutrophil death to plasma cytokine and histone levels, confirming the pathogenic role these molecules play during sepsis in humans.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Spyros Vernardis  

LAB HEAD: Markus Ralser

PROVIDER: PXD034391 | Pride | 2022-07-01

REPOSITORIES: Pride

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Publications


The mechanisms linking systemic infection to hyperinflammation and immune dysfunction in sepsis are poorly understood. Extracellular histones promote sepsis pathology, but their source and mechanism of action remain unclear. Here, we show that by controlling fungi and bacteria captured by splenic macrophages, neutrophil-derived myeloperoxidase attenuates sepsis by suppressing histone release. In systemic candidiasis, microbial capture via the phagocytic receptor SIGNR1 neutralizes myeloperoxidas  ...[more]

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