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

Feng, Xinwei; Lu, Junfeng; He, Zitian; Wang, Yidan; Qi, Fangfang; Zhang, Ge

doi:10.3389/fcimb.2018.00201

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…PC12 cells, a cell line from the rat pheochromocytoma of the adrenal medulla, have been extensively used as a mature neural cell model of neurite outgrowth [27][28][29]. In order to further validate the effect of the RhoA signaling pathway on neurite outgrowth, neuronally differentiated PC12 cells were treated with CT04 or Y27632 for 24 h. The results indicated that both CT04 and Y27632 treatments increased neurite outgrowth in neuronally differentiated PC12 cells ( Figure 2A-C,G,H).…”

Section: The Rhoa Pathway Negatively Regulates Neurite Outgrowth In Nmentioning

confidence: 97%

RhoA-GTPase Modulates Neurite Outgrowth by Regulating the Expression of Spastin and p60-Katanin

Tan

Zhang

Deng

et al. 2020

Cells

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RhoA-GTPase (RhoA) is widely regarded as a key molecular switch to inhibit neurite outgrowth by rigidifying the actin cytoskeleton. However, during neurite outgrowth, whether and how microtubule dynamics are regulated by RhoA remains to be elucidated. Herein, CT04 and Y27632 were used to inactivate RhoA and its downstream effector Rho-associated coiled coil-forming kinase (ROCK), while the RhoAQ63L lentiviral vector was utilized to overexpress the constitutively activated RhoA in dorsal root ganglion (DRG) neurons or neuronal differentiated PC12 cells. The current data illustrate that the RhoA signaling pathway negatively modulates neurite outgrowth and elevates the expression of Glu-tubulin (a marker for a stabilized microtubule). Meanwhile, the microtubule-severing proteins spastin and p60-katanin were downregulated by the RhoA signaling pathway. When spastin and p60-katanin were knocked down, the effects of RhoA inhibition on neurite outgrowth were significantly reversed. Taken together, this study demonstrates that the RhoA pathway-mediated inhibition of neurite outgrowth is not only related to the modulation of microfilament dynamics but is also attributable to the regulation of the expression of spastin and p60-katanin and thus influences microtubule dynamics.

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Section: The Rhoa Pathway Negatively Regulates Neurite Outgrowth In Nmentioning

confidence: 97%

RhoA-GTPase Modulates Neurite Outgrowth by Regulating the Expression of Spastin and p60-Katanin

Tan

Zhang

Deng

et al. 2020

Cells

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“…M. smegmatis infection of PC12 and C17.2 cells induces neural differentiation through an autophagy-independent pathway via IFN-γ and PI3K-Akt signaling pathways ( 92 ). Vitamin D3, known as a protective factor for human tuberculosis, increases intracellular M. smegmatis clearance and restricts host cell cytotoxicity ( 93 ).…”

Section: Autophagy In Ntm Infectionsmentioning

confidence: 99%

Autophagy and Host Defense in Nontuberculous Mycobacterial Infection

Silwal

Kim

2021

Front. Immunol.

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Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens via autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to Mycobacterium tuberculosis (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host–pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.

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“…The lipopolysaccharides mainly consist of lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol mannosides (PIMs) [27]. LAM, located on the cell envelope, is a crucial immunomodulatory compound that participates in host-pathogen interactions [28,29]. There are three kinds of arabinosyltransferase in mycobacteria, namely, EmbA, EmbB, and EmbC, which catalyze the transfer of arabinofuranose (Araf ) residues to different substrate molecules.…”

Section: Introductionmentioning

confidence: 99%

Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells

Liu

Gui

Chen

et al. 2022

Cells

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Mycobacterium tuberculosis (M. tb) is an intracellular pathogen persisting in phagosomes that has the ability to escape host immune surveillance causing tuberculosis (TB). Lipoarabinomannan (LAM), as a glycolipid, is one of the complex outermost components of the mycobacterial cell envelope and plays a critical role in modulating host responses during M. tb infection. Different species within the Mycobacterium genus exhibit distinct LAM structures and elicit diverse innate immune responses. However, little is known about the mechanisms. In this study, we first constructed a LAM-truncated mutant with fewer arabinofuranose (Araf) residues named M. sm-ΔM_6387 (Mycobacterium smegmatis arabinosyltransferase EmbC gene knockout strain). It exhibited some prominent cell wall defects, including tardiness of mycobacterial migration, loss of acid-fast staining, and increased cell wall permeability. Within alveolar epithelial cells (A549) infected by M. sm-ΔM_6387, the uptake rate was lower, phagosomes with bacterial degradation appeared, and microtubule-associated protein light chain 3 (LC3) recruitment was enhanced compared to wild type Mycobacterium smegmatis (M. smegmatis). We further confirmed that the variability in the removal capability of M. sm-ΔM_6387 resulted from host cell responses rather than the changes in the mycobacterial cell envelope. Moreover, we found that M. sm-ΔM_6387 or its glycolipid extracts significantly induced expression changes in some genes related to innate immune responses, including Toll-like receptor 2 (TLR2), class A scavenger receptor (SR-A), Rubicon, LC3, tumor necrosis factor alpha (TNF-α), Bcl-2, and Bax. Therefore, our studies suggest that nonpathogenic M. smegmatis can deposit LC3 on phagosomal membranes, and the decrease in the quantity of Araf residues for LAM molecules not only impacts mycobacterial cell wall integrity but also enhances host defense responses against the intracellular pathogens and decreases phagocytosis of host cells.

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

Cited by 4 publications

References 42 publications

RhoA-GTPase Modulates Neurite Outgrowth by Regulating the Expression of Spastin and p60-Katanin

RhoA-GTPase Modulates Neurite Outgrowth by Regulating the Expression of Spastin and p60-Katanin

Autophagy and Host Defense in Nontuberculous Mycobacterial Infection

Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells

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