Journal
SCIENCE IMMUNOLOGY
Volume 2, Issue 10, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aam8929
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Funding
- Canadian Institutes of Health Research (CIHR) [RS-342013]
- Department of Critical Care Medicine at the University of Calgary
- University of Calgary Medical Group
- Canada Foundation for Innovation John R. Evans Leaders fund
- Alberta Enterprise
- CIHR Team Grant: Health Challenges in Chronic Inflammation Initiative
- Dutch Lung Foundation [3.2.10.052]
- Advanced Education Research Capacity Program
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Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, up-regulation of host defense proteins through Toll-like receptors (TLRs) and nuclear factor kappa B requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88 (myeloid differentiation primary response gene 88)-dependent and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coil sequestered to the lung endothelium. Therefore, the lung capillaries provide a vascular defensive niche whereby endothelium and neutrophils cooperate for immediate detection and capture of disseminating pathogens.
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