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Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging te...

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Autores principales: Zhou, Hongli, Lu, Yuting, Wei, Hang, Chen, Yixin, Limpanon, Yanin, Dekumyoy, Paron, Huang, Ping, Shi, Peiyao, Lv, Zhiyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176765/
https://www.ncbi.nlm.nih.gov/pubmed/35617354
http://dx.doi.org/10.1371/journal.pntd.0010461
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author Zhou, Hongli
Lu, Yuting
Wei, Hang
Chen, Yixin
Limpanon, Yanin
Dekumyoy, Paron
Huang, Ping
Shi, Peiyao
Lv, Zhiyue
author_facet Zhou, Hongli
Lu, Yuting
Wei, Hang
Chen, Yixin
Limpanon, Yanin
Dekumyoy, Paron
Huang, Ping
Shi, Peiyao
Lv, Zhiyue
author_sort Zhou, Hongli
collection PubMed
description Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.
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spelling pubmed-91767652022-06-09 Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis Zhou, Hongli Lu, Yuting Wei, Hang Chen, Yixin Limpanon, Yanin Dekumyoy, Paron Huang, Ping Shi, Peiyao Lv, Zhiyue PLoS Negl Trop Dis Research Article Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC. Public Library of Science 2022-05-26 /pmc/articles/PMC9176765/ /pubmed/35617354 http://dx.doi.org/10.1371/journal.pntd.0010461 Text en © 2022 Zhou et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhou, Hongli
Lu, Yuting
Wei, Hang
Chen, Yixin
Limpanon, Yanin
Dekumyoy, Paron
Huang, Ping
Shi, Peiyao
Lv, Zhiyue
Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title_full Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title_fullStr Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title_full_unstemmed Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title_short Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis
title_sort stat3/il-6 signaling mediates sustained pneumonia induced by agiostrongylus cantonensis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176765/
https://www.ncbi.nlm.nih.gov/pubmed/35617354
http://dx.doi.org/10.1371/journal.pntd.0010461
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