Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice.
Cutaneous leishmaniasis caused by Leishmania major is an emergent, uncontrolled public health problem and there is no vaccine. A promising prophylactic approach has been immunotherapy with Toll-like receptor (TLR) agonists to enhance parasite-specific immune responses. We have previously reported th...
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ftdoajarticles:oai:doaj.org/article:2e9e6ae0b042421b96f41aa578204264 2023-05-15T15:09:39+02:00 Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. Lu Huang Meleana Hinchman Susana Mendez 2015-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003546 https://doaj.org/article/2e9e6ae0b042421b96f41aa578204264 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4354918?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003546 https://doaj.org/article/2e9e6ae0b042421b96f41aa578204264 PLoS Neglected Tropical Diseases, Vol 9, Iss 3, p e0003546 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003546 2022-12-31T13:05:48Z Cutaneous leishmaniasis caused by Leishmania major is an emergent, uncontrolled public health problem and there is no vaccine. A promising prophylactic approach has been immunotherapy with Toll-like receptor (TLR) agonists to enhance parasite-specific immune responses. We have previously reported that vaccination of C57BL/6 mice with live L. major plus the TLR9 agonist CpG DNA prevents lesion development and confers immunity to reinfection. Our current study aims to investigate whether other TLR agonists can be used in leishmanization without induction of lesion formation. We found that live L. major plus the TLR2 agonist Pam3CSK4 reduced the pathology in both genetically resistant (C57BL/6) and susceptible (BALB/c) mouse strains. The addition of Pam3CSK4 activated dermal dendritic cells and macrophages to produce greater amounts of proinflammatory cytokines in both mouse strains. Both Th1 and Th17 responses were enhanced by leishmanization with L. major plus Pam3CSK4 in C57BL/6 mice; however, Th17 cells were unchanged in BALB/c mice. The production of IL-17 from neutrophils was enhanced in both strains infected with L. major plus Pam3CSK4. However, the sustained influx of neutrophils in sites of infection was only observed in BALB/c mice. Our data demonstrate that the mechanism behind leishmanization with TLR agonists may be very different depending upon the immunological background of the host. This needs to be taken into account for the rational development of successful vaccines against the disease. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 3 e0003546 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Lu Huang Meleana Hinchman Susana Mendez Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Cutaneous leishmaniasis caused by Leishmania major is an emergent, uncontrolled public health problem and there is no vaccine. A promising prophylactic approach has been immunotherapy with Toll-like receptor (TLR) agonists to enhance parasite-specific immune responses. We have previously reported that vaccination of C57BL/6 mice with live L. major plus the TLR9 agonist CpG DNA prevents lesion development and confers immunity to reinfection. Our current study aims to investigate whether other TLR agonists can be used in leishmanization without induction of lesion formation. We found that live L. major plus the TLR2 agonist Pam3CSK4 reduced the pathology in both genetically resistant (C57BL/6) and susceptible (BALB/c) mouse strains. The addition of Pam3CSK4 activated dermal dendritic cells and macrophages to produce greater amounts of proinflammatory cytokines in both mouse strains. Both Th1 and Th17 responses were enhanced by leishmanization with L. major plus Pam3CSK4 in C57BL/6 mice; however, Th17 cells were unchanged in BALB/c mice. The production of IL-17 from neutrophils was enhanced in both strains infected with L. major plus Pam3CSK4. However, the sustained influx of neutrophils in sites of infection was only observed in BALB/c mice. Our data demonstrate that the mechanism behind leishmanization with TLR agonists may be very different depending upon the immunological background of the host. This needs to be taken into account for the rational development of successful vaccines against the disease. |
format |
Article in Journal/Newspaper |
author |
Lu Huang Meleana Hinchman Susana Mendez |
author_facet |
Lu Huang Meleana Hinchman Susana Mendez |
author_sort |
Lu Huang |
title |
Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
title_short |
Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
title_full |
Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
title_fullStr |
Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
title_full_unstemmed |
Coinjection with TLR2 agonist Pam3CSK4 reduces the pathology of leishmanization in mice. |
title_sort |
coinjection with tlr2 agonist pam3csk4 reduces the pathology of leishmanization in mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003546 https://doaj.org/article/2e9e6ae0b042421b96f41aa578204264 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 3, p e0003546 (2015) |
op_relation |
http://europepmc.org/articles/PMC4354918?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003546 https://doaj.org/article/2e9e6ae0b042421b96f41aa578204264 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003546 |
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PLOS Neglected Tropical Diseases |
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3 |
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e0003546 |
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