Abstract
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.
Highlights
The microbiome has tremendous potential to influence human physiology (Sharon et al, 2014)
Pathogenic M. tuberculosis and non-pathogenic M. bovis BCG were used as the slow-growing Mycobacteria controls
MTT assays revealed that infected PC12 and C17.2 cells exhibited a reduced cell viability in a time-dependent manner and in a dose-dependent manner, but more than 80% cells were still viable at 48 h post-infection (MOI:10:1) (Figure 1)
Summary
The microbiome has tremendous potential to influence human physiology (Sharon et al, 2014). Host-microbe interactions affect immunity, metabolism, development, and behavior (Vuong et al, 2017). Some bacteria can produce neuroactive metabolites, ranging from serotonin and γ-amino butyric acid, to dopamine and norepinephrine, to acetylcholine and histamine to influence the nervous system (Takahashi et al, 2012; Oleskin et al, 2017). Emerging researches have shown that dysbiosis of gut bacteria, commensal skin or other microbiota can affect host behavior by producing chemical signals or directly influencing host nervous systems (Ochoa-Reparaz and Kasper, 2014; Obata and Pachnis, 2016). Microbiota have been identified within immune-privileged sites such as the central nervous system (CNS). Proteobacteria and Actinobacteria are reported to be the major commensals persistent in
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