• Christian D Ellson, Rebecca Dunmore, Cory M Hogaboam, Matthew A Sleeman, and Lynne A Murray.
• 1 MedImmune Ltd, Granta Park, Cambridge, United Kingdom; and.
• Am. J. Respir. Cell Mol. Biol. 2014 Aug 1; 51 (2): 163-8.

AbstractThe chronic debilitating lung disease, idiopathic pulmonary fibrosis (IPF), is characterized by a progressive decline in lung function, with a median mortality rate of 2-3 years after diagnosis. IPF is a disease of unknown cause and progression, and multiple pathways have been demonstrated to be activated in the lungs of these patients. A recent genome-wide association study of more than 1,000 patients with IPF identified genes linked to host defense, cell-cell adhesion, and DNA repair being altered due to fibrosis (Fingerlin, et al. Nat Genet 2013;45:613-620). Further emerging data suggest that the respiratory system may not be a truly sterile environment, and it exhibits an altered microbiome during fibrotic disease (Molyneaux and Maher. Eur Respir Rev 2013;22:376-381). These altered host defense mechanisms might explain the increased susceptibility of patients with IPF to microbial- and viral-induced exacerbations. Moreover, chronic epithelial injury and apoptosis are key features in IPF, which might be mediated, in part, by both pathogen-associated (PA) and danger-associated molecular patterns (MPs). Emerging data indicate that both PAMPs and danger-associated MPs contribute to apoptosis, but not necessarily in a manner that allows for the removal of dying cells, without further exacerbating inflammation. In contrast, both types of MPs drive cellular necrosis, leading to an exacerbation of lung injury and/or infection as the debris promotes a proinflammatory response. Thus, this Review focuses on the impact of MPs resulting from infection-driven apoptosis and necrosis during chronic fibrotic lung disease.

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