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J Infect. 2015 Apr;70(4):415-26. doi: 10.1016/j.jinf.2014.09.013. Epub 2014 Oct 13.

MRP8/14 induces autophagy to eliminate intracellular Mycobacterium bovis BCG.

Author information

1
Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Department of Laboratory Medicine, Guangzhou First Municipal People's Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510500, China.
2
Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, China.
3
Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
4
Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
5
Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou 325035, China.
6
Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China. Electronic address: gdtb_bg@vip.163.com.
7
Department of Immunology, Institute of Tuberculosis Control, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: huangxi6@mail.sysu.edu.cn.

Abstract

OBJECTIVE:

To explore the role of myeloid-related protein 8/14 in mycobacterial infection.

METHODS:

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 Mycobacterium bovis 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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Autophagy; Bacterial killing; Mycobacterium bovis BCG; Myeloid-related protein 8/14

PMID:
25312864
DOI:
10.1016/j.jinf.2014.09.013
[Indexed for MEDLINE]

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