Myelin breakdown favours Mycobacterium leprae survival in Schwann cells

2019 ◽  
Vol 22 (1) ◽  
Author(s):  
Bruno Siqueira Mietto ◽  
Beatriz Junqueira Souza ◽  
Patricia Sammarco Rosa ◽  
Maria Cristina Vidal Pessolani ◽  
Flavio Alves Lara ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Mycobacterium Leprae ◽  
Myelin Breakdown

scholarly journals Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake of Mycobacterium leprae by Schwann Cells in Human Leprosy

2010 ◽  
Vol 78 (11) ◽  
pp. 4634-4643 ◽  
Author(s):  
Rosane M. B. Teles ◽  
Stephan R. Krutzik ◽  
Maria T. Ochoa ◽  
Rosane B. Oliveira ◽  
Euzenir N. Sarno ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Primary Cultures ◽  
Mycobacterium Leprae ◽  
Microbial Pathogens ◽  
Interleukin 4 ◽  
Common Mechanism ◽  
Specific Cell

ABSTRACT The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.

scholarly journals Structure-Guided Computational Approaches to Unravel Druggable Proteomic Landscape of Mycobacterium leprae

2021 ◽  
Vol 8 ◽  
Author(s):  
Sundeep Chaitanya Vedithi ◽  
Sony Malhotra ◽  
Marta Acebrón-García-de-Eulate ◽  
Modestas Matusevicius ◽  
Pedro Henrique Monteiro Torres ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Schwann Cells ◽  
Protein Structures ◽  
Mycobacterium Leprae ◽  
Data Bank ◽  
Nerve Damage ◽  
Structural Proteomics ◽  
Bacterial Survival ◽  
Functional Sites

Leprosy, caused by Mycobacterium leprae (M. leprae), is treated with a multidrug regimen comprising Dapsone, Rifampicin, and Clofazimine. These drugs exhibit bacteriostatic, bactericidal and anti-inflammatory properties, respectively, and control the dissemination of infection in the host. However, the current treatment is not cost-effective, does not favor patient compliance due to its long duration (12 months) and does not protect against the incumbent nerve damage, which is a severe leprosy complication. The chronic infectious peripheral neuropathy associated with the disease is primarily due to the bacterial components infiltrating the Schwann cells that protect neuronal axons, thereby inducing a demyelinating phenotype. There is a need to discover novel/repurposed drugs that can act as short duration and effective alternatives to the existing treatment regimens, preventing nerve damage and consequent disability associated with the disease. Mycobacterium leprae is an obligate pathogen resulting in experimental intractability to cultivate the bacillus in vitro and limiting drug discovery efforts to repositioning screens in mouse footpad models. The dearth of knowledge related to structural proteomics of M. leprae, coupled with emerging antimicrobial resistance to all the three drugs in the multidrug therapy, poses a need for concerted novel drug discovery efforts. A comprehensive understanding of the proteomic landscape of M. leprae is indispensable to unravel druggable targets that are essential for bacterial survival and predilection of human neuronal Schwann cells. Of the 1,614 protein-coding genes in the genome of M. leprae, only 17 protein structures are available in the Protein Data Bank. In this review, we discussed efforts made to model the proteome of M. leprae using a suite of software for protein modeling that has been developed in the Blundell laboratory. Precise template selection by employing sequence-structure homology recognition software, multi-template modeling of the monomeric models and accurate quality assessment are the hallmarks of the modeling process. Tools that map interfaces and enable building of homo-oligomers are discussed in the context of interface stability. Other software is described to determine the druggable proteome by using information related to the chokepoint analysis of the metabolic pathways, gene essentiality, homology to human proteins, functional sites, druggable pockets and fragment hotspot maps.

scholarly journals Evidence for phagosome-lysosome fusion in Mycobacterium leprae-infected murine Schwann cells.

1989 ◽  
Vol 57 (3) ◽  
pp. 1008-1010 ◽  
Author(s):  
U Steinhoff ◽  
J R Golecki ◽  
J Kazda ◽  
S H Kaufmann
Keyword(s):  
Schwann Cells ◽  
Mycobacterium Leprae

scholarly journals Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 198 ◽  
Author(s):  
Toshihiro Masaki ◽  
Aidan McGlinchey ◽  
Simon R. Tomlinson ◽  
Jinrong Qu ◽  
Anura Rambukkana
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Fate ◽  
Cell Lineage ◽  
Mycobacterium Leprae ◽  
Differentiation Markers ◽  
Primary Host ◽  
Transfer Property ◽  
Retention Capacity ◽  
Transfer Properties

Background: Bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. Recently, we have shown that Mycobacterium leprae (ML), the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult Schwann cells to progenitor/stem cell-like cells (pSLC) which appear to facilitate bacterial spread. Here, we studied how this cell fate change influences bacterial retention and transfer properties of Schwann cells before and after reprogramming.Results: Using primary fibroblasts as bacterial recipient cells, we showed that non-reprogrammed Schwann cells, which preserve all Schwann cell lineage and differentiation markers, possess high bacterial retention capacity when co-cultured with skin fibroblasts; Schwann cells failed to transfer bacteria to fibroblasts at higher numbers even after co-culture for 5 days. In contrast, pSLCs, which are derived from the same Schwann cells but have lost Schwann cell lineage markers due to reprogramming, efficiently transferred bacteria to fibroblasts within 24 hours.Conclusions: ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties. We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data also suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection.

scholarly journals Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

2008 ◽  
Vol 103 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Tatiana Pereira da Silva ◽  
Ana Caroline Costa da Silva ◽  
Maria da Graça Araújo Baruque ◽  
Rosane Barbosa de Oliveira ◽  
Marcelo Pelajo Machado ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Mycobacterium Leprae

Bacterial and host-derived cationic proteins bind α2-laminins and enhance Mycobacterium leprae attachment to human Schwann cells

2000 ◽  
Vol 2 (12) ◽  
pp. 1407-1417 ◽  
Author(s):  
Maria Angela de Melo Marques ◽  
Sebabrata Mahapatra ◽  
Devki Nandan ◽  
Thomas Dick ◽  
Euzenir Nunes Sarno ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Mycobacterium Leprae ◽  
Cationic Proteins

scholarly journals Innate Immune Response Precedes Mycobacterium leprae–Induced Reprogramming of Adult Schwann Cells

2014 ◽  
Vol 16 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Toshihiro Masaki ◽  
Aidan McGlinchey ◽  
Justyna Cholewa-Waclaw ◽  
Jinrong Qu ◽  
Simon R. Tomlinson ◽  
...  
Keyword(s):  
Immune Response ◽  
Schwann Cells ◽  
Innate Immune Response ◽  
Mycobacterium Leprae ◽  
Innate Immune
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