Cargando…
Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway
BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857240/ https://www.ncbi.nlm.nih.gov/pubmed/31727141 http://dx.doi.org/10.1186/s13071-019-3786-z |
_version_ | 1783470725854658560 |
---|---|
author | Wang, Hui Zhang, Chuan-Shan Fang, Bin-Bin Li, Zhi-De Li, Liang Bi, Xiao-Juan Li, Wen-Ding Zhang, Ning Lin, Ren-Yong Wen, Hao |
author_facet | Wang, Hui Zhang, Chuan-Shan Fang, Bin-Bin Li, Zhi-De Li, Liang Bi, Xiao-Juan Li, Wen-Ding Zhang, Ning Lin, Ren-Yong Wen, Hao |
author_sort | Wang, Hui |
collection | PubMed |
description | BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced by E. granulosus (s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear. METHODS: The activation status of peritoneal macrophages (PMs) derived from mice infected with E. granulosus (sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treated in vivo and in vitro with recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected. RESULTS: The expression of AAM-related genes in PMs was preferentially induced after E. granulosus (s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated from E. granulosus (s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained after E. granulosus (s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotype in vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor. CONCLUSIONS: This study demonstrates that E. granulosus (s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part, via the PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host. |
format | Online Article Text |
id | pubmed-6857240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68572402019-12-05 Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway Wang, Hui Zhang, Chuan-Shan Fang, Bin-Bin Li, Zhi-De Li, Liang Bi, Xiao-Juan Li, Wen-Ding Zhang, Ning Lin, Ren-Yong Wen, Hao Parasit Vectors Research BACKGROUND: Larvae of Echinococcus granulosus (sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced by E. granulosus (s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear. METHODS: The activation status of peritoneal macrophages (PMs) derived from mice infected with E. granulosus (sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treated in vivo and in vitro with recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected. RESULTS: The expression of AAM-related genes in PMs was preferentially induced after E. granulosus (s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated from E. granulosus (s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained after E. granulosus (s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotype in vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor. CONCLUSIONS: This study demonstrates that E. granulosus (s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part, via the PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host. BioMed Central 2019-11-14 /pmc/articles/PMC6857240/ /pubmed/31727141 http://dx.doi.org/10.1186/s13071-019-3786-z Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Wang, Hui Zhang, Chuan-Shan Fang, Bin-Bin Li, Zhi-De Li, Liang Bi, Xiao-Juan Li, Wen-Ding Zhang, Ning Lin, Ren-Yong Wen, Hao Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title | Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title_full | Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title_fullStr | Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title_full_unstemmed | Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title_short | Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway |
title_sort | thioredoxin peroxidase secreted by echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via pi3k/akt/mtor pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857240/ https://www.ncbi.nlm.nih.gov/pubmed/31727141 http://dx.doi.org/10.1186/s13071-019-3786-z |
work_keys_str_mv | AT wanghui thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT zhangchuanshan thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT fangbinbin thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT lizhide thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT liliang thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT bixiaojuan thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT liwending thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT zhangning thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT linrenyong thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway AT wenhao thioredoxinperoxidasesecretedbyechinococcusgranulosussensustrictopromotesthealternativeactivationofmacrophagesviapi3kaktmtorpathway |