Chronic obstructive pulmonary disease (COPD) is a disease defined by an aberrant inflammatory response to inhaled cigarette smoke and other noxious particles. The factors triggered in the lungs that drive inflammation and lung tissue destruction are not fully understood, but mononuclear phagocytes play a central role by releasing mediators that promote both inflammation and tissue-destructive emphysema. Although conflicting studies on alveolar macrophages exist regarding chronic cigarette smoke exposure and its effects on macrophage polarization patterns, we have recently identified a cell type in mice defined by CX3CR1 expression. The population of this cell type expands in the lungs and elaborates M1 signature cytokines in response to cigarette smoke exposure in vivo. In addition, the absence of functional CX3CR1 provides protection from tissue-destructive emphysema in a murine model of chronic cigarette smoke exposure. The heterogeneity and plasticity of discrete macrophage subsets, in terms of immunophenotype and function, may explain the seemingly disparate findings showing a suppressed inflammatory profile on the one hand and a heightened inflammatory response on the other. This review examines the evidence that discrete mononuclear phagocyte subsets develop in response to cigarette smoke exposure, and that the spatial cues provided by the lung tissue microenvironment in which the mononuclear phagocytes reside may influence the distribution and function of these subsets.
- Pattern recognition receptors