Lung Microbes Promote Pulmonary Fibrosis In Mice

Chinese researchers have uncovered how lung microbiota produce outer membrane vesicles to trigger a host immune response that causes pathological progression of pulmonary fibrosis.

AsianScientist (Mar. 15, 2019) – In a study published in Immunity, a team of scientists in China has identified two types of bacteria in the lung that exacerbate pulmonary fibrosis.

Mucosal microbiota is actively being investigated for its important roles in host immunity. Scientists are just beginning to understand how bacteria found in the body, such as those in the intestine and lungs, are involved in health and disease.

In the present study, researchers led by Professor Qian Youcun at the Shanghai Institute of Nutrition and Health, China, used high-throughput sequencing to discover that there was relatively abundant microbiota in mouse lung tissue under homeostasis. However, in the pathological tissues of mice with pulmonary fibrosis, the microbiota was obviously disordered, which was crucial for the pathogenesis of pulmonary fibrosis.

When systematically analyzing the changes in microbiota of the lungs of mice with pulmonary fibrosis, the researchers noticed that bacteroides and prevotella were significantly increased in the disease state. They also demonstrated that the microorganisms could secrete outer membrane vesicles (OMVs) to drive the production of an inflammatory protein called interleukin-17B (IL-17B).

Using bone marrow transplantation, cell sorting and other experimental methods, the researchers further showed that IL-17B was mainly produced by alveolar macrophages. The molecule directly acts on lung epithelial cells to induce the expression of downstream genes that promote the recruitment of neutrophils and the differentiation of Th17 cells. The influx of immune cells to the lungs thus results in the development of pulmonary inflammation and fibrosis.

The researchers hope that their findings will provide therapeutic targets for the clinical treatment of pulmonary fibrosis and associated diseases caused by dysregulated microbiota.

The article can be found at: Yang et al. (2019) Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles.


Source: Chinese Academy of Sciences.
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