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Sci Immunol. 2017 Apr 28;2(10). pii: eaam8929. doi: 10.1126/sciimmunol.aam8929.

The Lung is a Host Defense Niche for Immediate Neutrophil-Mediated Vascular Protection.

Author information

1
Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
2
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
3
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
4
Mouse Phenomics Resource Laboratory, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
5
Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
6
Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
7
Department of Intensive Care, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
8
Department of Blood Cell Research, Sanquin Research, and Landsteiner Laboratory, Amsterdam, The Netherlands.
9
Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands.
10
Departments of Medicine and Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSW512, California 94143-0511, USA.
11
Department of Pathology, University of California, San Francisco, 513 Parnassus Ave, HSW512, San Francisco, California 94143-0511, USA.

Abstract

Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-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 coli 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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