Therapeutic enhancement of protective immunity during experimental leishmaniasis.
Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between ef...
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ftdoajarticles:oai:doaj.org/article:62202b358aa84460976bb87d98af3fa4 2023-05-15T15:08:42+02:00 Therapeutic enhancement of protective immunity during experimental leishmaniasis. Senad Divanovic Aurelien Trompette Jamie I Ashworth Marepalli B Rao Christopher L Karp 2011-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001316 https://doaj.org/article/62202b358aa84460976bb87d98af3fa4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3167777?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001316 https://doaj.org/article/62202b358aa84460976bb87d98af3fa4 PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1316 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001316 2022-12-31T13:43:46Z Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+) T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx), a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+) T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 9 e1316 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
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 Senad Divanovic Aurelien Trompette Jamie I Ashworth Marepalli B Rao Christopher L Karp Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+) T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx), a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+) T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline. |
format |
Article in Journal/Newspaper |
author |
Senad Divanovic Aurelien Trompette Jamie I Ashworth Marepalli B Rao Christopher L Karp |
author_facet |
Senad Divanovic Aurelien Trompette Jamie I Ashworth Marepalli B Rao Christopher L Karp |
author_sort |
Senad Divanovic |
title |
Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
title_short |
Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
title_full |
Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
title_fullStr |
Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
title_full_unstemmed |
Therapeutic enhancement of protective immunity during experimental leishmaniasis. |
title_sort |
therapeutic enhancement of protective immunity during experimental leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001316 https://doaj.org/article/62202b358aa84460976bb87d98af3fa4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 9, p e1316 (2011) |
op_relation |
http://europepmc.org/articles/PMC3167777?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001316 https://doaj.org/article/62202b358aa84460976bb87d98af3fa4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001316 |
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PLoS Neglected Tropical Diseases |
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5 |
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9 |
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e1316 |
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1766340003284123648 |