On Oct. 16, Prof. Ge Baoxue’s team from Tongji University School of Medicine and Shanghai Pulmonary Hospital affiliated to Tongji University, published their research in Nature Communications that Mycobacterium tuberculosis inhibits endoplasmic calcium ion channel protein CACNA2D3 in host macrophages by upregulating expression of miR-27a and thus reduces calcium signal dependent autophagy to facilitate survival and infection of Mycobacterium tuberculosis.  

To explore novel mechanisms of Mycobacterium tuberculosis infection and pathogenesis, Prof. Baoxue Ge’s team conducted in-depth sequencing of macrophages infected by Mycobacterium tuberculosis and other samples from Mycobacterium tuberculosis infected mice and patients. They found that Mycobacterium tuberculosis infection dramatically upregulates expression of miR-27a, which significantly inhibits autophagy and promotes survival of Mycobacterium tuberculosis and exacerbation of tuberculosis. Further study showed that miR-27a targets endoplasmic ion channel CACNA2D3 and inhibits expression of CACNA2D3 gene, disrupting calcium signals and autophagy pathway in host cells and facilitating survival and infection of Mycobacterium tuberculosis. Finally, inhibitors of miR-27a effectively ameliorated pathological pulmonary lesion caused by Mycobacterium tuberculosis infection and reduced pulmonary bacteria load. This work revealed a novel immune evasion pathway that Mycobacterium tuberculosis inhibits calcium signal dependent autophagy by inducing host miR-27a as theoretical foundation of tuberculosis diagnosis and therapy. Meanwhile, an inhibitor of miR-27a as a novel anti-tuberculosis drug is in process of patent filing and development.

The first authors are Dr. Liu Feng, research assistant Jianxia Chen and attending physician Wang Peng from Shanghai Pulmonary Hospital. The correspondence author is Prof. Ge Baoxue from Shanghai Pulmonary Hospital.

Prof. Ge Baoxue is Director of Shanghai Key Lab of Tuberculosis. The lab relies on Shanghai Pulmonary Hospital affiliated to Tongji University and focuses on basic and clinical translational research of tuberculosis prevention, diagnosis and therapy. This work was supported by National Basic Research Program of China, Key Program and Major Research Program of NNSF and Key Clinical Discipline Construction Program of Shanghai Municipality

Link：https://www.nature.com/articles/s41467-018-06836-4