Role of CD14 in lung inflammation and infection

Abstract

This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855.

Figure 1

Central role of CD14 in pathogen- and pathogen-associated molecular pattern (PAMP)-induced responses in the lung. CD14, which lacks an intracellular domain for signal transduction, is expressed on the surface of alveolar macrophages, infiltrating monocytes and neutrophils, and at lower levels also on epithelial and endothelial cells in the lung. CD14 recognizes and binds various structures from invading microbes, such as lipopolysaccharide (LPS) from Gram-negative bacteria, lipoteichoic acid (LTA) from Gram-positive bacteria, lipoarabinomannan (LAM) from mycobacteria, viral double stranded (ds) RNA and F glycoprotein (F-gp) from respiratory syncytial virus (RSV). CD14 subsequently transfers these bound components to Toll-like receptors (TLR) which than trigger cell activation. Binding of LPS to CD14 is regulated by additional accessory receptors in the lung, including LPS-binding protein (LBP) and a number of surfactant proteins (SP). Furthermore, soluble CD14 (sCD14) enhances LPS-induced activation of cells with low CD14 expression. Depending on the microbe and the PAMPs it expresses, CD14-amplified responses can either be beneficial to the host by induction of an adequate inflammatory and immune response to eradicate the invading microbe, or detrimental to the host by excessive inflammation and/or dissemination of the pathogen.