MRP8/14 induces autophagy to eliminate intracellular Mycobacterium bovis BCG. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Wang, Jinli; Huang, Chunyu; Wu, Minhao; Zhong, Qiu; Yang, Kun; Li, Miao; Zhan, Xiaoxia; Wen, Jinsheng; Zhou, Lin; Huang, Xi
• Is Part Of: Journal of infection. Volume 70:Issue 4(2015)
• Page Start: 415
• Page End: 426
• Publication Date: 2015-04
• Subjects: Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2014.09.013
• Languages: English
• ISSNs: 0163-4453

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Summary</title> <sec> <title id="sectitle0015">Objective</title> <p id="abspara0010">To explore the role of myeloid-related protein 8/14 in mycobacterial infection.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">The mRNA and protein expression levels of MRP8 or MRP14 were measured by real-time PCR and flow cytometry, respectively. Role of MRP8/14 was tested by overexpression or RNA interference assays. Flow cytometry and colony forming unit were used to test the phagocytosis and the survival of intracellular <italic>Mycobacterium bovis</italic> BCG (BCG), respectively. Autophagy mediated by MRP8/14 was detected by Western blot and immunofluorescence. The colocalization of BCG phagosomes with autophagosomes or lysosomes was by detected by confocal microscopy. ROS production was detected by flow cytometry.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">MRP8/14 expressions were up-regulated in human monocytic THP1 cells and primary macrophages after mycobacterial challenge. Silencing of MRP8/14 suppressed bacterial killing, but had no influence on the phagocytosis of BCG. Importantly, silencing MRP8/14 decreased autophagy and BCG phagosome maturation in THP1-derived macrophages, thereby increasing the BCG survival. Additionally, we demonstrated that MRP8/14 promoted autophagy in a ROS-dependent manner.</p> </sec> <sec> <title id="sectitle0030">Conclusions</title> <p id="abspara0025">The present study revealed a novel role of MRP8/14 in the autophagy-mediated elimination of intracellular BCG by promoting ROS generation, which may provide a promising therapeutic target for tuberculosis and other intracellular bacterial infectious diseases.</p> </sec> </abstract>