Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Silva, Tatiana Oliveira da; Silva, Ana Caroline Costa da; Baruque, Maria da Graca Araujo; Oliveira, Rosane B. de; Pelajo-Machado, Marcelo; Sarno, Euzenir Nunes

doi:10.1590/s0074-02762008000400009

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…Our results indicate that SW-10 cells show similar phenotypes in response to M . leprae infection, as shown in primary Schwann cells and in ST88-14 cells, which is the myelinating Schwann cell line (Table 1) [35]. The results of this study suggest that M .…”

Section: Discussionsupporting

confidence: 63%

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The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

Jin

Lee

2017

PLoS Negl Trop Dis

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Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.

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Section: Discussionsupporting

confidence: 63%

“…M . leprae infection induces apoptosis in ST88-14 cells, a human Schwann cell line [35]. In addition, treatment with M .…”

Section: Discussionmentioning

confidence: 99%

The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

Jin

Lee

2017

PLoS Negl Trop Dis

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“…S6B ). In the case of SP‐01, cells presented Schwann cell characteristics such as bipolar or tripolar morphology with oval nuclei [ 64 ] and were positive for all four markers (Fig. 4A,B , Table 3 ), compatible with a melanoma cell line [ 65 , 66 , 67 , 68 ].…”

Section: Resultsmentioning

confidence: 99%

Expanding a precision medicine platform for malignant peripheral nerve sheath tumors: New patient‐derived orthotopic xenografts, cell lines and tumor entities

Creus‐Bachiller,

Fernández‐Rodríguez,

Magallón‐Lorenz

et al. 2023

Molecular Oncology

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Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with a poor survival rate, presenting either sporadically or in the context of neurofibromatosis type 1 (NF1). The histological diagnosis of MPNSTs can be challenging, with different tumors exhibiting great histological and marker expression overlap. This heterogeneity could be partly responsible for the observed disparity in treatment response due to the inherent diversity of the preclinical models used. For several years, our group has been generating a large patient‐derived orthotopic xenograft (PDOX) MPNST platform for identifying new precision medicine treatments. Herein, we describe the expansion of this platform using six primary tumors clinically diagnosed as MPNSTs, from which we obtained six additional PDOX mouse models and three cell lines, thus generating three pairs of in vitro–in vivo models. We extensively characterized these tumors and derived preclinical models, including genomic, epigenomic and histological analyses. Tumors were reclassified after these analyses: three remained as MPNSTs (two being classic MPNSTs), one was a melanoma, another an Neurotrophic tyrosine receptor kinase (NTRK)‐rearranged spindle cell neoplasm, and, finally, an unclassifiable tumor bearing Neurofibromin‐2 (NF2) inactivation, an Neuroblastoma RAS Viral Oncogene Homolog (NRAS) oncogenic mutation and a SWI/SNF‐related Matrix associated Actin‐dependent Regulator of Chromatin (SMARCA4) heterozygous truncated variant. New cell lines and PDOXs faithfully recapitulated histology, marker expression and genomic characteristics of the primary tumors. The diversity in tumor identity and their specific associated genomic alterations impacted on treatment responses obtained when we used the new cell lines for testing compounds against known altered pathways in MPNSTs. In summary, we present here an extension of our MPNST precision medicine platform, with new PDOXs and cell lines, including tumor entities confounded as MPNSTs in a real clinical scenario. This platform may constitute a useful tool for obtaining correct preclinical information to guide MPNST clinical trials.

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“…Human Schwann cells of the ST8814 lineage (RRID: CVCL_8916) were donated by Dr. Jonathan Fletcher (Harvard University). This cell lineage is an immortalized human non-myelinating phagocytic Schwann glial cell, expressing S100, GFAP, MBP, ninjurin, laminin, and CD44 (Silva et al, 2008). Schwann cells were cultured in RPMI medium (Thermo Fisher Scientific;Cat# 31800-022) supplemented with 10% fetal bovine serum (FBS; Cripion; Cat# FB0010S) and maintained at 37°C in an atmosphere of 5% CO 2 for no more than 100 passages.…”

Section: Cell Culture and Treatment With Akt Inhibitor And L-lactatementioning

confidence: 99%

Phenolic glycolipid‐1 of Mycobacterium leprae is involved in human Schwann cell line ST8814 neurotoxic phenotype

Vasconcelos

Mietto

Lima

et al. 2022

Journal of Neurochemistry

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Leprosy is a chronic infectious disease caused by Mycobacterium leprae infection in Schwann cells. Axonopathy is considered a hallmark of leprosy neuropathy and is associated with the irreversible motor and sensory loss seen in infected patients.Although M. leprae is recognized to provoke Schwann cell dedifferentiation, the mechanisms involved in the contribution of this phenomenon to neural damage remain unclear. In the present work, we used live M. leprae to infect the immortalized human Schwann cell line ST8814. The neurotoxicity of infected Schwann cell-conditioned medium (SCCM) was then evaluated in a human neuroblastoma cell lineage and mouse neurons. ST8814 Schwann cells exposed to M. leprae affected neuronal viability by deviating glial 14 C-labeled lactate, important fuel of neuronal central metabolism, to de novo lipid synthesis. The phenolic glycolipid-1 (PGL-1) is a specific M. leprae cell wall antigen proposed to mediate bacterial-Schwann cell interaction. Therefore, we assessed the role of the PGL-1 on Schwann cell phenotype by using transgenic M. bovis (BCG)-expressing the M. leprae PGL-1. We observed that BCG-PGL-1 was able to induce a phenotype similar to M. leprae, unlike the wild-type BCG strain. We next demonstrated that this Schwann cell neurotoxic phenotype, induced by M. leprae PGL-1, occurs through the protein kinase B (Akt) pathway. Interestingly, the pharmacological inhibition of Akt by triciribine significantly reduced free fatty acid content in the SCCM from M. leprae-and BCG-PGL-1-infected Schwann cells and, hence, preventing neuronal death. Overall, these findings provide novel evidence that both M. leprae and PGL-1, induce a toxic Schwann cell phenotype, by modifying the host lipid metabolism, resulting in profound implications for neuronal loss. We consider this metabolic rewiring a new molecular mechanism to be the basis of leprosy neuropathy.

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Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Cited by 9 publications

References 29 publications

The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

Expanding a precision medicine platform for malignant peripheral nerve sheath tumors: New patient‐derived orthotopic xenografts, cell lines and tumor entities

Phenolic glycolipid‐1 of Mycobacterium leprae is involved in human Schwann cell line ST8814 neurotoxic phenotype

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