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Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages

In host defense, it is crucial to maintain the acidity of the macrophage phagosome for effective bacterial clearance. However, the mechanisms governing phagosomal acidification upon exposure to gram-negative bacteria have not been fully elucidated. In this study, we demonstrate that in macrophages e...

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Autores principales: Yoon, Sung-Jin, Jo, Dong Hyun, Park, Seung-Ho, Park, Jun-Young, Lee, Yoo-Kyung, Lee, Moo-Seung, Min, Jeong-Ki, Jung, Haiyoung, Kim, Tae-Don, Yoon, Suk Ran, Chung, Su Wol, Kim, Jeong Hun, Choi, Inpyo, Park, Young-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861186/
https://www.ncbi.nlm.nih.gov/pubmed/31781121
http://dx.doi.org/10.3389/fimmu.2019.02636
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author Yoon, Sung-Jin
Jo, Dong Hyun
Park, Seung-Ho
Park, Jun-Young
Lee, Yoo-Kyung
Lee, Moo-Seung
Min, Jeong-Ki
Jung, Haiyoung
Kim, Tae-Don
Yoon, Suk Ran
Chung, Su Wol
Kim, Jeong Hun
Choi, Inpyo
Park, Young-Jun
author_facet Yoon, Sung-Jin
Jo, Dong Hyun
Park, Seung-Ho
Park, Jun-Young
Lee, Yoo-Kyung
Lee, Moo-Seung
Min, Jeong-Ki
Jung, Haiyoung
Kim, Tae-Don
Yoon, Suk Ran
Chung, Su Wol
Kim, Jeong Hun
Choi, Inpyo
Park, Young-Jun
author_sort Yoon, Sung-Jin
collection PubMed
description In host defense, it is crucial to maintain the acidity of the macrophage phagosome for effective bacterial clearance. However, the mechanisms governing phagosomal acidification upon exposure to gram-negative bacteria have not been fully elucidated. In this study, we demonstrate that in macrophages exposed to Escherichia coli, the thioredoxin-interacting protein (TXNIP)-associated inflammasome plays a role in pH modulation through the activated caspase-1-mediated inhibition of NADPH oxidase. While there was no difference in early-phase bacterial engulfment between Txnip knockout (KO) macrophages and wild-type (WT) macrophages, Txnip KO macrophages were less efficient at destroying intracellular bacteria in the late phase, and their phagosomes failed to undergo appropriate acidification. These phenomena were associated with reactive oxygen species production and were reversed by treatment with an NADPH oxidase inhibitor or a caspase inhibitor. In line with these results, Txnip KO mice were more susceptible to both intraperitoneally administered E. coli and sepsis induced by cecum ligation and puncture than WT mice. Taken together, this study suggests that the TXNIP-associated inflammasome-caspase-1 axis regulates NADPH oxidase to modulate the pH of the phagosome, controlling bacterial clearance by macrophages.
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spelling pubmed-68611862019-11-28 Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages Yoon, Sung-Jin Jo, Dong Hyun Park, Seung-Ho Park, Jun-Young Lee, Yoo-Kyung Lee, Moo-Seung Min, Jeong-Ki Jung, Haiyoung Kim, Tae-Don Yoon, Suk Ran Chung, Su Wol Kim, Jeong Hun Choi, Inpyo Park, Young-Jun Front Immunol Immunology In host defense, it is crucial to maintain the acidity of the macrophage phagosome for effective bacterial clearance. However, the mechanisms governing phagosomal acidification upon exposure to gram-negative bacteria have not been fully elucidated. In this study, we demonstrate that in macrophages exposed to Escherichia coli, the thioredoxin-interacting protein (TXNIP)-associated inflammasome plays a role in pH modulation through the activated caspase-1-mediated inhibition of NADPH oxidase. While there was no difference in early-phase bacterial engulfment between Txnip knockout (KO) macrophages and wild-type (WT) macrophages, Txnip KO macrophages were less efficient at destroying intracellular bacteria in the late phase, and their phagosomes failed to undergo appropriate acidification. These phenomena were associated with reactive oxygen species production and were reversed by treatment with an NADPH oxidase inhibitor or a caspase inhibitor. In line with these results, Txnip KO mice were more susceptible to both intraperitoneally administered E. coli and sepsis induced by cecum ligation and puncture than WT mice. Taken together, this study suggests that the TXNIP-associated inflammasome-caspase-1 axis regulates NADPH oxidase to modulate the pH of the phagosome, controlling bacterial clearance by macrophages. Frontiers Media S.A. 2019-11-12 /pmc/articles/PMC6861186/ /pubmed/31781121 http://dx.doi.org/10.3389/fimmu.2019.02636 Text en Copyright © 2019 Yoon, Jo, Park, Park, Lee, Lee, Min, Jung, Kim, Yoon, Chung, Kim, Choi and Park. http://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 Immunology
Yoon, Sung-Jin
Jo, Dong Hyun
Park, Seung-Ho
Park, Jun-Young
Lee, Yoo-Kyung
Lee, Moo-Seung
Min, Jeong-Ki
Jung, Haiyoung
Kim, Tae-Don
Yoon, Suk Ran
Chung, Su Wol
Kim, Jeong Hun
Choi, Inpyo
Park, Young-Jun
Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title_full Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title_fullStr Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title_full_unstemmed Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title_short Thioredoxin-Interacting Protein Promotes Phagosomal Acidification Upon Exposure to Escherichia coli Through Inflammasome-Mediated Caspase-1 Activation in Macrophages
title_sort thioredoxin-interacting protein promotes phagosomal acidification upon exposure to escherichia coli through inflammasome-mediated caspase-1 activation in macrophages
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861186/
https://www.ncbi.nlm.nih.gov/pubmed/31781121
http://dx.doi.org/10.3389/fimmu.2019.02636
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