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Background  Intracellular 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.    Methods  IRAK-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.    Results  IRAK-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.    Conclusions  Conclusively, 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 .

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