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