IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis

BMC Microbiology

Research Article

Xinjie Zhai¹  Hanju Huang¹  Chunwei Shi¹  Fei Hong¹  Jilei Ma¹  Maopeng Tian¹  Jianrong Li¹  Pei Shen²  Quan Li³ 

[1] Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People’s Republic of China;Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, People’s Republic of China;Department of Clinical Microbiology, School of Public Health, Taishan Medical University, 271016, Tai’an, People’s Republic of China;Wuhan Institute for Tuberculosis Control, 430030, Wuhan, People’s Republic of China;

关键词: Mycobacterium tuberculosis;    IRAK-M;    Macrophage;    Polarization;    Intracellular survival;   

DOI  :  10.1186/s12866-017-1095-2

 received in 2016-12-08, accepted in 2017-08-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIntracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction.MethodsIRAK-M expression was detected in M. tb infected macrophages and in human lung tissue of pulmonary tuberculosis with immunofluorescence staining, Western blot and immunohistochemistry. IRAK-M knock-down and over-expressing cell strains were constructed and intracellular survival of M. tb was investigated by acid-fast staining and colony forming units. Molecular markers of M1-type (pSTAT1 and iNOS) and M2-type (pSTAT6 and Arg-1) macrophages were detected using Western blot in IRAK-M knockdown U937 cells infected with M. tb H37Rv. U937 cells were stimulated with immunostimulant CpG7909 into M1 status and then infected with M. tb H37Rv. Expression of IRAK-M, IRAK-4 and iNOS was detected with immunofluorescence staining and Western blot, to evaluate the effect of IRAK-M to CpG directed M1-type polarization of macrophages during M. tb infection. Molecules related with macrophage’s bactericidal ability such as Hif-1 and phosphorylated ERK1/2 were detected with immunohistochemistry and Western blot.ResultsIRAK-M increased in M. tb infected macrophage cells and also in human lung tissue of pulmonary tuberculosis. IRAK-M over-expression resulted in higher bacterial load, while IRAK-M interference resulted in lower bacterial load in M. tb infected cells. During M. tb infection, IRAK-M knockdown induced M1-type, while inhibited M2-type polarization of macrophage. M1-type polarization of U937 cells induced by CpG7909 was inhibited by M. tb infection, which was reversed by IRAK-M knockdown in U937 cells. IRAK-M affected Hif-1 and MAPK signaling cascade during M. tb infection.ConclusionsConclusively, IRAK-M might alter the polarity of macrophages, to facilitate intracellular survival of M. tb and affect Th1-type immunity of the host, which is helpful to understanding the pathogenesis of M. tb.

【 授权许可】

CC BY   
© The Author(s). 2017