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Both pathogenic and non-pathogenic  Mycobacteria  can induce the differentiation of immune cells into dendritic cells (DC) or DC-like cells. In addition, pathogenic  Mycobacteria  is found to stimulate cell differentiation in the nerves system. Whether non-pathogenic  Mycobacteria  interacts with nerve cells remains unknown. In this study, we found that co-incubation with fast-growing  Mycobacteria smegmatis  induced neuron-like morphological changes of PC12 and C17.2 cells. Moreover, the  M. smegmatis  culture supernatant which was ultrafiltrated through a membrane with a 10 kDa cut-off, induced neurite outgrowth and differentiation in an autophagy-independent pathway in PC12 and C17.2 cells. Further analysis showed that IFN-γ production and activation of the PI3K-Akt signaling pathway were involved in the neural differentiation. In conclusion, our finding demonstrated that non-pathogenic  M. smegmatis  was able to promote neuronal differentiation by its extracellular proteins, which might provide a novel therapeutic strategy for the treatment of neurodegenerative disorders.

Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells