Natural killer cells in infection and inflammation of the lung

Abstract

The lungs are a major site of entry of pathogens into the body and thus require rapid and effective innate responses to prevent pathogens establishing infection and to limit their spread. Additionally, the immune response in the lung must be tightly regulated such that pathogens are cleared, but immunopathology and chronic inflammation are prevented. In this review, I consider the role of natural killer (NK) cells in pulmonary infection and inflammation, specifically their contributions to influenza, tuberculosis, asthma and chronic obstructive pulmonary disease (COPD), which are major causes of morbidity and mortality world-wide. Despite evidence of the importance of NK cells in these diseases, there are still major gaps in our understanding of how their function is regulated in this unique tissue environment. Understanding how different beneficial and detrimental effector functions of NK cells are triggered will be crucial if NK cells are to be exploited therapeutically in respiratory disease.

Figure 1

Potential activating and inhibitory interactions of natural killer (NK) cells in the lung. NK cell function in the lung is regulated by both contact-dependent interactions and soluble mediators. Note that, although many of these interactions have been demonstrated in vitro, their timing, location and relative importance in vivo are not known. HA, haemagglutinin; IFN, interferon; IL, interleukin; KIR, killer immunoglobulin-like receptor; MICA, MHC class I polypeptide-related sequence A; MHC, major histocompatibility complex; TGF, transforming growth factor; ULBP, UL16-binding protein.