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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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010461","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T17:55:46Z","timestamp":1653587746000},"page":"e0010461","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stat3\/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis"],"prefix":"10.1371","volume":"16","author":[{"given":"Hongli","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanin","family":"Limpanon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paron","family":"Dekumyoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1792-2805","authenticated-orcid":true,"given":"Zhiyue","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"pntd.0010461.ref001","doi-asserted-by":"crossref","first-page":"e0007951","DOI":"10.1371\/journal.pntd.0007951","article-title":"Schistosome migration in the definitive host","volume":"14","author":"CS Nation","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010461.ref002","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.parint.2007.04.002","article-title":"A long and winding road: the Plasmodium sporozoite\u2019s journey in the mammalian host","volume":"56","author":"P Sinnis","year":"2007","journal-title":"Parasitol Int"},{"key":"pntd.0010461.ref003","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/S0041-0101(96)00091-8","article-title":"Toxins produced by arthropod parasites: salivary gland proteins of human body lice and venom proteins of chelonine wasps","volume":"34","author":"D Jones","year":"1996","journal-title":"Toxicon"},{"key":"pntd.0010461.ref004","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1007\/s00436-017-5472-4","article-title":"Study on the tolerance and adaptation of rats to Angiostrongylus cantonensis infection","volume":"116","author":"L Ji","year":"2017","journal-title":"Parasitol Res"},{"key":"pntd.0010461.ref005","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1365-3024.1984.tb00785.x","article-title":"Ultrastructural evidence for eosinophil-mediated destruction of Angiostrongylus cantonensis transferred into the pulmonary artery of non-permissive hosts","volume":"6","author":"K Yoshimura","year":"1984","journal-title":"Parasite Immunol"},{"key":"pntd.0010461.ref006","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0020-7519(75)90091-0","article-title":"Comparative studies on the life history of Angiostrongylus mackerrasae Bhaibulaya, 1968 and Angiostrongylus cantonensis (Chen, 1935).","volume":"5","author":"M. 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