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A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965344/ https://www.ncbi.nlm.nih.gov/pubmed/35369443 http://dx.doi.org/10.3389/fmicb.2022.803041 |
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author | Chiang, Chih-Yuan Lane, Douglas J. Zou, Yefen Hoffman, Tim Pan, Jianfeng Hampton, Janice Maginnis, Jillian Nayak, Bishnu P. D’Oro, Ugo Valiante, Nicholas Miller, Andrew T. Cooke, Michael Wu, Tom Bavari, Sina Panchal, Rekha G. |
author_facet | Chiang, Chih-Yuan Lane, Douglas J. Zou, Yefen Hoffman, Tim Pan, Jianfeng Hampton, Janice Maginnis, Jillian Nayak, Bishnu P. D’Oro, Ugo Valiante, Nicholas Miller, Andrew T. Cooke, Michael Wu, Tom Bavari, Sina Panchal, Rekha G. |
author_sort | Chiang, Chih-Yuan |
collection | PubMed |
description | Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam(3)CSK(4) (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium. |
format | Online Article Text |
id | pubmed-8965344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89653442022-03-31 A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis Chiang, Chih-Yuan Lane, Douglas J. Zou, Yefen Hoffman, Tim Pan, Jianfeng Hampton, Janice Maginnis, Jillian Nayak, Bishnu P. D’Oro, Ugo Valiante, Nicholas Miller, Andrew T. Cooke, Michael Wu, Tom Bavari, Sina Panchal, Rekha G. Front Microbiol Microbiology Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam(3)CSK(4) (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8965344/ /pubmed/35369443 http://dx.doi.org/10.3389/fmicb.2022.803041 Text en Copyright © 2022 Chiang, Lane, Zou, Hoffman, Pan, Hampton, Maginnis, Nayak, D’Oro, Valiante, Miller, Cooke, Wu, Bavari and Panchal. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Chiang, Chih-Yuan Lane, Douglas J. Zou, Yefen Hoffman, Tim Pan, Jianfeng Hampton, Janice Maginnis, Jillian Nayak, Bishnu P. D’Oro, Ugo Valiante, Nicholas Miller, Andrew T. Cooke, Michael Wu, Tom Bavari, Sina Panchal, Rekha G. A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title | A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title_full | A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title_fullStr | A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title_full_unstemmed | A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title_short | A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis |
title_sort | novel toll-like receptor 2 agonist protects mice in a prophylactic treatment model against challenge with bacillus anthracis |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965344/ https://www.ncbi.nlm.nih.gov/pubmed/35369443 http://dx.doi.org/10.3389/fmicb.2022.803041 |
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