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

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.

Tissue‐resident innate immunity in the lung

“…5 However, it is important to remember that innate immune cells can also be tissue-resident and are vital in providing the first line of defence against inhaled allergens and pathogens. 10,11 Macrophages In mice, lung development starts as early as 9 days after conception, but lungs remain sterile until birth. In this review, we focus on lung-resident innate immune subsets of haematopoietic origin that are long-lived and often maintained long-term through self-renewal.…”

Unraveling the host's immune response to infection: Seeing is believing

“…At steady state, lung‐resident neutrophils are found crawling inside the capillaries and are in constant contact with the lung endothelium. A recent study by Yipp et al . sought to understand the dynamic relationship between these resident immune cells and the endothelium.…”

Unintended effects of drug carriers: Big issues of small particles

“…The marginated pool is largest in the lungs; e.g., 70% of neutrophils in rabbits are in the pulmonary marginated pool [236]. This marginated pool of pulmonary intravascular neutrophils has been shown to form a defensive barrier, capturing pathogens such as bacteria very rapidly after their introduction into the blood [237]. Future studies are needed to determine whether the marginated pool of neutrophils also takes up NPs, how pathology plays a role, and whether such NP uptake leads to either positive or negative consequences.…”

“…Illustration of pulmonary intravascular macrophages (PIMs) and marginated neutrophils that can phagocytose a significant amount of IV-injected nanoparticles are presented in capillaries adjacent to alveoli [229–237]. …”