The role of natural killer cells in pulmonary immunosurveillance

Abstract

Natural killer (NK) cells were originally identified as lymphocytes capable of killing cancer cells without prior sensitization (1). Further characterization of these cells in both humans and rodent models has expanded their role towards a broad-based immunosurveillance of diseased and healthy peripheral tissues. Among peripheral organs, the lung contains the largest percentage of NK cells. Accordingly, NK cells are implicated in many immunological responses within the lung, including innate effector functions as well as initiation of the adaptive immune response. In this article, we review the characteristics of NK cells, current models of NK maturation and cell activation, migration of NKs to the lung, and effector functions of NKs in cancer and infection in the airways. Specific emphasis is placed on the functional significance of NKs in cancer immunosurveillance. Therapeutic modulation of NK cells appears to be a challenging but promising approach to limit cancer, inflammation, and infection in the lung.

Investigation of opioid use and long-term oncologic outcomes for non-small cell lung cancer patients treated with surgery

“…The lung contains the largest percentage of NK cells among the peripheral organs [14], and the postoperative period is known as the ‘decisive period,’ when NK cell-mediated immunity suppresses emerging lung cancer metastasis [15, 16]. Based on these assumptions, a previous study by Maher et al [8] reported that a group of 99 recurrent patients who underwent VATS lung cancer surgery had greater postoperative opioid use than the non-recurrent group.…”

Viral–bacterial interactions in the respiratory tract

“…They then contribute to antiviral immunity by killing infected host cells, regulating T-cell function and secreting interferon (IFN-g) (Hesker & Krupnick, 2013). NK cells additionally contribute to clearance of pneumococcal infection through interaction with infected macrophages and dendritic cells (Elhaik-Goldman et al, 2011;Hesker & Krupnick, 2013;Mandelboim et al, 2001). Decreased numbers of NK cells in the lung and impaired NK cell function after influenza infection of mice have been shown to impair innate responses against S. aureus infection by contributing to a lack of activation of AMs (Small et al, 2010).…”

“…NK cells can recognize viral structures on infected cells and respond to stress signals released by the infected host. They then contribute to antiviral immunity by killing infected host cells, regulating T-cell function and secreting interferon (IFN-g) (Hesker & Krupnick, 2013). NK cells additionally contribute to clearance of pneumococcal infection through interaction with infected macrophages and dendritic cells (Elhaik-Goldman et al, 2011;Hesker & Krupnick, 2013;Mandelboim et al, 2001).…”

Natural Killer Cells and Innate Interferon Gamma Participate in the Host Defense against Respiratory Vaccinia Virus Infection

“…Among peripheral tissues, the lung contains the largest percentage of NK cells, indicating potential crucial involvement of NK cells in respiratory infections (22). Indeed, NK cells have been implicated in early defense against several viral (respiratory syncytial virus [RSV] and influenza) and bacterial (Mycobacterium tuberculosis and Bordetella pertussis) pathogens that cause pneumonia (23)(24)(25). NK cells may participate in defense against respiratory pathogens via various mechanisms, including direct lysis of infected cells, production of chemokines that amplify the host's inflammatory response, production of antiviral cytokines, such as IFN-␥ and tumor necrosis factor alpha (TNF), and activation of DCs that mediate T cell differentiation and trafficking to the lung (23,26).…”

“…Indeed, NK cells have been implicated in early defense against several viral (respiratory syncytial virus [RSV] and influenza) and bacterial (Mycobacterium tuberculosis and Bordetella pertussis) pathogens that cause pneumonia (23)(24)(25). NK cells may participate in defense against respiratory pathogens via various mechanisms, including direct lysis of infected cells, production of chemokines that amplify the host's inflammatory response, production of antiviral cytokines, such as IFN-␥ and tumor necrosis factor alpha (TNF), and activation of DCs that mediate T cell differentiation and trafficking to the lung (23,26). In some instances, particularly during more severe respiratory infections, NK cells can be responsible for acute lung immune injury and mortality (27)(28)(29).…”