Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection.
BACKGROUND: Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clea...
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ftdoajarticles:oai:doaj.org/article:61e658b992504d9688351ad0dcef2868 2023-05-15T15:12:13+02:00 Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. Teresa G Martins Gabriela Trigo Alexandra G Fraga José B Gama Adhemar Longatto-Filho Margarida Saraiva Manuel T Silva António G Castro Jorge Pedrosa 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001925 https://doaj.org/article/61e658b992504d9688351ad0dcef2868 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3510087?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0001925 https://doaj.org/article/61e658b992504d9688351ad0dcef2868 PLoS Neglected Tropical Diseases, Vol 6, Iss 11, p e1925 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001925 2022-12-31T13:18:25Z BACKGROUND: Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX). Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of corticosteroids or other immunosuppressive/anti-inflammatory drugs for ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 11 e1925 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Teresa G Martins Gabriela Trigo Alexandra G Fraga José B Gama Adhemar Longatto-Filho Margarida Saraiva Manuel T Silva António G Castro Jorge Pedrosa Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX). Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of corticosteroids or other immunosuppressive/anti-inflammatory drugs for ... |
format |
Article in Journal/Newspaper |
author |
Teresa G Martins Gabriela Trigo Alexandra G Fraga José B Gama Adhemar Longatto-Filho Margarida Saraiva Manuel T Silva António G Castro Jorge Pedrosa |
author_facet |
Teresa G Martins Gabriela Trigo Alexandra G Fraga José B Gama Adhemar Longatto-Filho Margarida Saraiva Manuel T Silva António G Castro Jorge Pedrosa |
author_sort |
Teresa G Martins |
title |
Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
title_short |
Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
title_full |
Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
title_fullStr |
Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
title_full_unstemmed |
Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection. |
title_sort |
corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine mycobacterium ulcerans infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001925 https://doaj.org/article/61e658b992504d9688351ad0dcef2868 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 11, p e1925 (2012) |
op_relation |
http://europepmc.org/articles/PMC3510087?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0001925 https://doaj.org/article/61e658b992504d9688351ad0dcef2868 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001925 |
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PLoS Neglected Tropical Diseases |
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6 |
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11 |
container_start_page |
e1925 |
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1766342939135442944 |