Stage-specific remodeling of the pulmonary microenvironment during Paragonimus proliferus infection in a rat model
- 1Yunnan Provincial Key Laboratory of Public Health and Biosafety & Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, PR China
- 2School of Medicine, Yunnan University, Kunming, Yunnan, PR China
- 3Department of Anesthesiology, Kunming Medical University First Clinical College, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China
Abstract
Paragonimiasis, a food-borne zoonosis caused by Paragonimus spp., can cause severe pulmonary inflammation and fibrosis. However, relationships among the host, parasite and lung microbiome at defined infection stages remain poorly understood. We compared independent groups of rats sampled at 14, 28 and 42 days post-infection (dpi), together with a separate group sampled after triclabendazole (TCBZ) treatment. Histopathological and molecular analyses were combined with multi-region (5R) 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH). Groups sampled at later post-infection time points showed greater pulmonary inflammation and collagen deposition, with the highest values in Pp-42d; both outcomes were lower in Pp-TCBZ than in Pp-42d. Th1-, eosinophil-, Th2- and Treg- associated markers differed among experimental groups. TLR4/NF-κB -related protein expression and pulmonary microbial profiles also differed among groups including enrichment of taxa such as Lactobacillus in infected animals. FISH detected bacterial signals within inflammatory lesions and Lactobacillus-associated signals spatially associated with parasite eggs. These repeated cross-sectional findings identify stage-associated differences in pulmonary pathology, immune markers and microbiota during P. proliferus infection, together with lower pathological measures in the Pp-TCBZ group than in the untreated Pp-42d group. The egg-associated bacterial signals warrant further investigation but do not establish a functional host-parasite-microbiome mechanism. Author summary: Paragonimiasis is a food-borne parasitic disease caused by lung flukes (Paragonimus species). It can resemble tuberculosis, which may delay appropriate treatment and contribute to lung damage. In this study, we compared separate groups of rats sampled at 14, 28 and 42 days after infection with Paragonimus proliferus, together with a separate group sampled after treatment with triclabendazole. Rats sampled at later post-infection time points had more extensive lung inflammation and scarring, with the greatest abnormalities in the 42-day group. The treated group had less pathological injury than the untreated 42-day group. Markers associated with several immune-response profiles, the TLR4/NF-κB pathway and the lung microbiome differed among the experimental groups. Fluorescence microscopy also detected Lactobacillus associated signals near parasite eggs. However, this spatial association does not establish a functional interaction. Overall, our findings provide a group-level description of pulmonary pathology, immune markers, and microbial profiles in independent rat groups sampled at selected infection stages and identify questions for future mechanistic investigation.
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BibTeX
@article{cheng2026stagespecific,
title = {{Stage-specific remodeling of the pulmonary microenvironment during Paragonimus proliferus infection in a rat model}},
author = {Danhong Cheng and Lei Zhang and Le Sun and Min Yin and Yu Wang and Shuwen Yang and Xing Yan and Xiaoyan Zhu and Cuiying Li and Weixun Chunyu},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = sep,
doi = {10.1371/journal.pntd.0014760},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014760},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Stage-specific remodeling of the pulmonary microenvironment during Paragonimus proliferus infection in a rat model
AU - Danhong Cheng
AU - Lei Zhang
AU - Le Sun
AU - Min Yin
AU - Yu Wang
AU - Shuwen Yang
AU - Xing Yan
AU - Xiaoyan Zhu
AU - Cuiying Li
AU - Weixun Chunyu
PY - 2026
DA - 2026/09/25
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014760
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014760
AB - Paragonimiasis, a food-borne zoonosis caused by Paragonimus spp., can cause severe pulmonary inflammation and fibrosis. However, relationships among the host, parasite and lung microbiome at defined infection stages remain poorly understood. We compared independent groups of rats sampled at 14, 28 and 42 days post-infection (dpi), together with a separate group sampled after triclabendazole (TCBZ) treatment. Histopathological and molecular analyses were combined with multi-region (5R) 16S rRNA gene sequencing and fluorescence in situ hybridization (FISH). Groups sampled at later post-infection time points showed greater pulmonary inflammation and collagen deposition, with the highest values in Pp-42d; both outcomes were lower in Pp-TCBZ than in Pp-42d. Th1-, eosinophil-, Th2- and Treg- associated markers differed among experimental groups. TLR4/NF-κB -related protein expression and pulmonary microbial profiles also differed among groups including enrichment of taxa such as Lactobacillus in infected animals. FISH detected bacterial signals within inflammatory lesions and Lactobacillus-associated signals spatially associated with parasite eggs. These repeated cross-sectional findings identify stage-associated differences in pulmonary pathology, immune markers and microbiota during P. proliferus infection, together with lower pathological measures in the Pp-TCBZ group than in the untreated Pp-42d group. The egg-associated bacterial signals warrant further investigation but do not establish a functional host-parasite-microbiome mechanism. Author summary: Paragonimiasis is a food-borne parasitic disease caused by lung flukes (Paragonimus species). It can resemble tuberculosis, which may delay appropriate treatment and contribute to lung damage. In this study, we compared separate groups of rats sampled at 14, 28 and 42 days after infection with Paragonimus proliferus, together with a separate group sampled after treatment with triclabendazole. Rats sampled at later post-infection time points had more extensive lung inflammation and scarring, with the greatest abnormalities in the 42-day group. The treated group had less pathological injury than the untreated 42-day group. Markers associated with several immune-response profiles, the TLR4/NF-κB pathway and the lung microbiome differed among the experimental groups. Fluorescence microscopy also detected Lactobacillus associated signals near parasite eggs. However, this spatial association does not establish a functional interaction. Overall, our findings provide a group-level description of pulmonary pathology, immune markers, and microbial profiles in independent rat groups sampled at selected infection stages and identify questions for future mechanistic investigation.
SN - 1935-2735
ER -