Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis

CD Ellson, R Dunmore, CM Hogaboam… - American journal of …, 2014 - atsjournals.org
CD Ellson, R Dunmore, CM Hogaboam, MA Sleeman, LA Murray
American journal of respiratory cell and molecular biology, 2014atsjournals.org
The 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 …
The 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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