Stat3/IL-6 signaling mediates sustained pneumonia induced by Angiostrongylus cantonensis
Issued Date
2022-05-01
Resource Type
ISSN
19352727
eISSN
19352735
Scopus ID
2-s2.0-85131038318
Pubmed ID
35617354
Journal Title
PLoS Neglected Tropical Diseases
Volume
16
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS Neglected Tropical Diseases Vol.16 No.5 (2022)
Suggested Citation
Zhou H., Lu Y., Wei H., Chen Y., Limpanon Y., Dekumyoy P., Huang P., Shi P., Lvid Z. Stat3/IL-6 signaling mediates sustained pneumonia induced by Angiostrongylus cantonensis. PLoS Neglected Tropical Diseases Vol.16 No.5 (2022). doi:10.1371/journal.pntd.0010461 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/87309
Title
Stat3/IL-6 signaling mediates sustained pneumonia induced by Angiostrongylus cantonensis
Author(s)
Other Contributor(s)
Abstract
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 dem-onstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analy-sis, 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 nonper-missive 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.