The role of c-Myc in phagocytosis of mycobacteria in human macrophages

Abstract

Tuberculosis remains a major cause of morbidity and mortality worldwide as a result of Mycobacterium tuberculosis infection. Macrophages are the major immunocytes to initiate host immunity against mycobacteria. Among the multiple strategies employed by macrophages to inhibit mycobacteria growth or kill intracellular mycobacteria, phagocytosis is the first step. Phagocytosis involves recognition, internalization and finally digestion of pathogens at phagolysosome. c-Myc is a transcription factor that regulates a variety of target genes. It can form a complex with Max and bind to the enhancer box sequences of the promoter to mediate the transcription. Recently, our group revealed that c-Myc has a potential role in regulating the antimicrobial responses in macrophages. Here, we further revealed that c-Myc may play a positive role in phagocytosis and contribute to host defense to mycobacteria. We demonstrated that mycobacteria could induce c-Myc expression in primary human macrophages. Using colony forming unit assay and cell imaging assay, we showed that pretreatment of c-Myc inhibitor, 10058-F4, could significantly reduce the amount of mycobacteria internalized by macrophages. In addition, the acidification of phagolysosome in mycobacteria infected macrophages was shown to be inhibited by 10058-F4. However, the action of c-Myc in the process of phagocytosis is independent of Rho family GTPases. In conclusion, c-Myc may play a role in phagocytosis of mycobacteria.