Pulmonary natural killer cells control neutrophil intravascular motility and response to acute inflammation

Abstract

The pulmonary immune system defends a huge surface area directly in contact with the contents of the air we breathe. Neutrophils, the most abundant immune cell in the pulmonary vasculature, are critical to immunity but they are also capable of generating life-threatening pathology. Natural Killer cells are the most highly represented lymphocyte subset in the lung, but relatively little is known about their localization, motility or the specific mechanisms by which they contribute to local homeostasis. Here, we used lung-intravital microscopy to directly visualise and quantify neutrophil and natural killer cell dynamics in the pulmonary vasculature of live mice. This approach revealed unexpected sessile behaviour by intravascular natural killer cells. Interactions with natural killer cells made neutrophils scan the endothelium more slowly over larger distances and reduced the number of neutrophils that accumulated in an LPS-triggered inflammatory challenge. This represents a new paradigm by which natural killer cells contribute to lung physiology by diminishing potentially pathogenic neutrophil accumulation.