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Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis

BACKGROUND: Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contrib...

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Autores principales: Kau, Jyh-Hwa, Sun, Der-Shan, Huang, Hsuan-Shun, Lien, Te-Sheng, Huang, Hsin-Hsien, Lin, Hung-Chi, Chang, Hsin-Hou
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000823/
https://www.ncbi.nlm.nih.gov/pubmed/21170330
http://dx.doi.org/10.1371/journal.pone.0014289
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author Kau, Jyh-Hwa
Sun, Der-Shan
Huang, Hsuan-Shun
Lien, Te-Sheng
Huang, Hsin-Hsien
Lin, Hung-Chi
Chang, Hsin-Hou
author_facet Kau, Jyh-Hwa
Sun, Der-Shan
Huang, Hsuan-Shun
Lien, Te-Sheng
Huang, Hsin-Hsien
Lin, Hung-Chi
Chang, Hsin-Hou
author_sort Kau, Jyh-Hwa
collection PubMed
description BACKGROUND: Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field. METHODOLOGY/PRINCIPAL FINDINGS: Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells. CONCLUSION/SIGNIFICANCE: These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection.
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spelling pubmed-30008232010-12-17 Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis Kau, Jyh-Hwa Sun, Der-Shan Huang, Hsuan-Shun Lien, Te-Sheng Huang, Hsin-Hsien Lin, Hung-Chi Chang, Hsin-Hou PLoS One Research Article BACKGROUND: Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field. METHODOLOGY/PRINCIPAL FINDINGS: Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells. CONCLUSION/SIGNIFICANCE: These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection. Public Library of Science 2010-12-10 /pmc/articles/PMC3000823/ /pubmed/21170330 http://dx.doi.org/10.1371/journal.pone.0014289 Text en Kau et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kau, Jyh-Hwa
Sun, Der-Shan
Huang, Hsuan-Shun
Lien, Te-Sheng
Huang, Hsin-Hsien
Lin, Hung-Chi
Chang, Hsin-Hou
Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title_full Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title_fullStr Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title_full_unstemmed Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title_short Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis
title_sort sublethal doses of anthrax lethal toxin on the suppression of macrophage phagocytosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000823/
https://www.ncbi.nlm.nih.gov/pubmed/21170330
http://dx.doi.org/10.1371/journal.pone.0014289
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