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

Bryan G. Yipp, Jung Hwan Kim, Ronald Lima, Lori D. Zbytnuik, Bjӧrn Petri, Nick Swanlund, May Ho, Vivian G. Szeto, Tamar Tak, Leo Koenderman, Peter Pickkers, Anton T. J. Tool, Taco W. Kuijpers, Timo K. van den Berg, Mark R. Looney, Matthew F. Krummel, Paul Kubes

Research output: Contribution to journalArticleAcademicpeer-review

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 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 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.
Original languageEnglish
Article numbereaam8929
JournalScience immunology
Volume2
Issue number10
DOIs
Publication statusPublished - 2017

Cite this

Yipp, B. G., Kim, J. H., Lima, R., Zbytnuik, L. D., Petri, B., Swanlund, N., ... Kubes, P. (2017). The lung is a host defense niche for immediate neutrophil-mediated vascular protection. Science immunology, 2(10), [eaam8929]. https://doi.org/10.1126/sciimmunol.aam8929