Research ArticleSEPSIS

The lung is a host defense niche for immediate neutrophil-mediated vascular protection

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Science Immunology  28 Apr 2017:
Vol. 2, Issue 10, eaam8929
DOI: 10.1126/sciimmunol.aam8929

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Neutrophils get their blood up

Capillaries in the lung are critical for gas exchange. Now, Yipp et al. report that lung capillaries also contribute to host defense against bloodstream pathogens. They found that vascular neutrophils immediately responded to the presence of endotoxin or bloodstream infection by sequestering within the capillaries but not larger venules. These neutrophils were activated through TLR4 and MyD88 signaling, polarized, and crawled throughout the endothelium, removing lung-sequestered bacteria from circulation. Thus, pulmonary capillaries form a neutrophil niche to capture blood-borne pathogens in the lung.

Abstract

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 κB 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 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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