Neutrophil ageing is regulated by the microbiome
By Dachuan Zhang, Grace Chen, D. Manwani, A. Mortha, Chunliang Xu, Jeremiah J. Faith, R. Burk, Y. Kunisaki, Jungeun Jang, C. Scheiermann and 2 more. Nature, 2015
752 citations recorded by the source corpus.
Blood polymorphonuclear neutrophils provide immune protection against pathogens, but may also promote tissue injury in inflammatory diseases. Although neutrophils are generally considered to be a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and replenishment by newly released neutrophils from the bone marrow. Aged neutrophils upregulate CXCR4, a receptor allowing their clearance in the bone marrow, with feedback inhibition of neutrophil production via the IL-17/G-CSF axis, and rhythmic modulation of the haematopoietic stem-cell niche. The aged subset also expresses low levels of L-selectin. Previous studies have suggested that in vitro-aged neutrophils exhibit impaired migration and reduced pro-inflammatory properties. Here, using in vivo ageing analyses in mice, we show that neutrophil pro-inflammatory activity correlates positively with their ageing whilst in circulation. Aged neutrophils represent an overly active subset exhibiting enhanced αMβ2 integrin activation and neutrophil extracellular trap formation under inflammatory conditions. Neutrophil ageing is driven by the microbiota via Toll-like receptor and myeloid differentiation factor 88-mediated signalling pathways. Depletion of the microbiota significantly reduces the number of circulating aged neutrophils and dramatically improves the pathogenesis and inflammation-related organ damage in models of sickle-cell disease or endotoxin-induced septic shock. These results identify a role for the microbiota in regulating a disease-promoting neutrophil subset.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/75b796012e403326ff73ff12afbe5d83a3edcc76
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In Immunology
Citations in the corpus
- Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? (2018, background): “Opposite to this, the mouse neutrophil marker Ly6G was also reduced in aged cells (Zhang et al., 2015) (Figure 3).”
- Homeostatic immunity and the microbiota (2017, positive): “The level of circulating innate cells, such as basophil, is also influenced by the microbiota, and tonic sensing of TLR ligands can promotes neutrophil “ageing” (Hill et al., 2012; Zhang et al., 2015).”
- Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “In mouse models of sick e-cell disease and endotoxin-induced sepsis, depletion of the gut microbiota, significantly reduced the number of ci rculating aged neutrophils and lessened organ damage (73).”