American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2017
Extracellular Mitochondrial DNA is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) involves the accumulation of α-smooth muscle actin-expressing myofibroblasts arising from interactions with soluble mediators such as transforming growth factor-β1 (TGF-β1) and mechanical influences such as local tissue stiffness. Whereas IPF fibroblasts are enriched for aerobic glycolysis and innate immune receptor activation, innate immune ligands related to mitochondrial injury, such as extracellular mitochondrial DNA (mtDNA), have not been identified in IPF. ⋯ These findings demonstrate a previously unrecognized and highly novel connection between metabolic reprogramming, mtDNA, fibroblast activation, and clinical outcomes that provides new insight into IPF.
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Am. J. Respir. Crit. Care Med. · Dec 2017
Whole Exome Sequencing Identify the 6q12-q16 Linkage Region and a Candidate Gene TTK for Pulmonary Nontuberculous Mycobacterial Disease.
Pulmonary nontuberculous mycobacterial disease (PNTM) often affects white postmenopausal women, with a tall and lean body habitus and higher rates of scoliosis, pectus excavatum, mitral valve prolapse, and mutations in the CFTR gene. These clinical features and the familial clustering of the disease suggest an underlying genetic mechanism. ⋯ The TTK gene encodes a protein kinase that is essential for mitotic checkpoints and the DNA damage response. TTK and other genetic loci identified in our study may contribute to the increased susceptibility to NTM infection and its progression to pulmonary disease.
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Am. J. Respir. Crit. Care Med. · Dec 2017
Maturation of the Infant Respiratory Microbiota, Environmental Drivers and Health Consequences: A Prospective Cohort Study.
Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. ⋯ Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.
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Am. J. Respir. Crit. Care Med. · Dec 2017
A Recombinant Fragment of Human Surfactant Protein D Suppresses Basophil Activation, Th2 and B Cell Responses in Grass Pollen-induced Allergic Inflammation.
Recombinant fragment of human surfactant protein D (rfhSP-D) has been shown to suppress house dust mite- and Aspergillus fumigatus-induced allergic inflammation in murine models. ⋯ For the first time, to our knowledge, we show that rfhSP-D inhibited allergen-induced basophil responses at a single-cell level and suppressed CD23-mediated facilitated allergen presentation and Th2 cytokine production. In addition, rfhSP-D inhibited IgE synthesis by B cells, which is also a novel observation.