Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy
Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infecti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.861586/full |
| _version_ | 1818264912850321408 |
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| author | Beatriz Junqueira de Souza Mayara Abud Mendes Gilberto Marcelo Sperandio da Silva Patrícia Sammarco-Rosa Milton Ozorio de Moraes Marcia Rodrigues Jardim Euzenir Nunes Sarno Roberto Olmo Pinheiro Bruno Siqueira Mietto |
| author_facet | Beatriz Junqueira de Souza Mayara Abud Mendes Gilberto Marcelo Sperandio da Silva Patrícia Sammarco-Rosa Milton Ozorio de Moraes Marcia Rodrigues Jardim Euzenir Nunes Sarno Roberto Olmo Pinheiro Bruno Siqueira Mietto |
| author_sort | Beatriz Junqueira de Souza |
| collection | DOAJ |
| description | Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment. |
| first_indexed | 2024-12-12T19:42:27Z |
| format | Article |
| id | doaj.art-f9397b5d0cc94770bf5e5027431564dd |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-12T19:42:27Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-f9397b5d0cc94770bf5e5027431564dd2022-12-22T00:14:10ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-04-01910.3389/fmed.2022.861586861586Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy NeuropathyBeatriz Junqueira de Souza0Mayara Abud Mendes1Gilberto Marcelo Sperandio da Silva2Patrícia Sammarco-Rosa3Milton Ozorio de Moraes4Marcia Rodrigues Jardim5Euzenir Nunes Sarno6Roberto Olmo Pinheiro7Bruno Siqueira Mietto8Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilClinical Research Laboratory in Chagas Disease, Evandro Chagas National Institute of Infectious Diseases, Fiocruz, Rio de Janeiro, BrazilLaboratory Animal House, Lauro de Souza Lima Institute, Sao-Paulo, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilLeprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, BrazilLaboratory of Cell Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, BrazilPeripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.https://www.frontiersin.org/articles/10.3389/fmed.2022.861586/fullleprosyMycobacterium lepraeperipheral nervous systemSchwann cellhost-pathogen interaction |
| spellingShingle | Beatriz Junqueira de Souza Mayara Abud Mendes Gilberto Marcelo Sperandio da Silva Patrícia Sammarco-Rosa Milton Ozorio de Moraes Marcia Rodrigues Jardim Euzenir Nunes Sarno Roberto Olmo Pinheiro Bruno Siqueira Mietto Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy Frontiers in Medicine leprosy Mycobacterium leprae peripheral nervous system Schwann cell host-pathogen interaction |
| title | Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy |
| title_full | Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy |
| title_fullStr | Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy |
| title_full_unstemmed | Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy |
| title_short | Gene Expression Profile of Mycobacterium leprae Contribution in the Pathology of Leprosy Neuropathy |
| title_sort | gene expression profile of mycobacterium leprae contribution in the pathology of leprosy neuropathy |
| topic | leprosy Mycobacterium leprae peripheral nervous system Schwann cell host-pathogen interaction |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.861586/full |
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