Lung natural killer cells in mice: phenotype and response to respiratory infection

Abstract

SummaryNatural killer (NK) cells have a specialized function in peripheral organs, which is determined by the organ-specific niches. We have attempted to explore whether lung NK cells display a particular phenotype according to their function in the unique pulmonary environment in health or during respiratory infection in mice. In healthy mice, higher frequencies of NK cells among lymphocytes were detected in the lung than in other tissues (lymph node, bone marrow, spleen, blood and liver), and lung NK cells maintained a more mature phenotype, implying that lung NK cells were critical for the pulmonary immune response. However, lung NK cells expressed higher levels of inhibitory receptors and lower levels of activating receptors, migration/adhesion-associated molecules and co-stimulatory molecules than splenic NK cells, implying that lung NK cells were quiescent, and the activation of lung NK cells was tightly regulated by the pulmonary environment in health. During respiratory infection, lung NK cells could be activated and express functional molecules (CD107a and interferon-c) to take part in the response to infection quickly. These results suggested that the unique pulmonary environment promotes the development of NK cells with a lung-specific phenotype.

Microbiota Modulate Tumoral Immune Surveillance in Lung through a γδT17 Immune Cell-Dependent Mechanism

“…Lymphocytes from the lung, liver, and spleen were isolated as previously described (18). The lymphocytes from the liver and lung were prepared by density gradient centrifugation with 40% and 70% Percoll.…”

Klebsiella pneumoniae Alleviates Influenza-Induced Acute Lung Injury via Limiting NK Cell Expansion

“…In the lung, NK cells make up the highest percentage of resident lymphocytes compared with any other tissue (12,13), suggesting that quick and effective NKmediated immune responses are critical for eliminating pathogens and maintaining homeostasis in the lung. Indeed, activation of lung NK cells promotes adaptive immune function and the elimination of viruses during influenza virus infection.…”

NK cells in immunotolerant organs

“…More specifically, pulmonary NK cells express a variety of Ly49 receptors, while the majority of NK cells derived from bone marrow progenitors express CD94 2 NKG2 heterodimers instead of Ly49 receptors, suggesting the possible influence of the lung microenvironment on the development of NK cells. 28 During a respiratory infection, pulmonary NK cells are activated and respond to infections swiftly by expressing functional molecules such as CD107a and IFN-c. 9 The production of tumor-necrosis factor is enhanced by pulmonary NK cells after infection with S. aureus. In the lung, alveolar macrophage-derived IL-15 supports NK cell proliferation and concurrently, the engulfment of S. aureus by lung macrophages is enhanced by the presence of NK cells.…”

“…9 Lungderived NK cells differ from bone marrow-derived NK cell progenitors due to the expression of the NK cell receptor Ly49 family. More specifically, pulmonary NK cells express a variety of Ly49 receptors, while the majority of NK cells derived from bone marrow progenitors express CD94 2 NKG2 heterodimers instead of Ly49 receptors, suggesting the possible influence of the lung microenvironment on the development of NK cells.…”

“…7 The lung is in danger of environmentally acquired infections and attacks from pathogens and bacteria due to its constant exposure to airborne pathogens. 8,9 Due to the importance of immune regulation in pregnancy, it is not surprising that the uterus is the most immunotolerant organ in the body. 10 These organs rely on microorganisms and their own organ-specific immunotolerant features to maintain moderate levels of immune responses and thus to sustain adequate growth and survival.…”