Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells.
Trichomonas vaginalis (TV) is a flagellated parasite that causes trichomoniasis, the most common non-viral sexually transmitted infection (STI), with over 275 million cases annually. TV has been shown to secrete extracellular vesicles (TV-EVs) to regulate intercellular communication between parasite...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013216 |
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| author | Ching-Yun Huang Shu-Fang Chiu Lichieh Julie Chu Yuan-Ming Yeh Po-Jung Huang Kuo-Lun Lan Yu-Ling Tsai Ching-Chun Liu Chien-Fu F Chen Wei-Ning Lin Kuo-Yang Huang |
| author_facet | Ching-Yun Huang Shu-Fang Chiu Lichieh Julie Chu Yuan-Ming Yeh Po-Jung Huang Kuo-Lun Lan Yu-Ling Tsai Ching-Chun Liu Chien-Fu F Chen Wei-Ning Lin Kuo-Yang Huang |
| author_sort | Ching-Yun Huang |
| collection | DOAJ |
| description | Trichomonas vaginalis (TV) is a flagellated parasite that causes trichomoniasis, the most common non-viral sexually transmitted infection (STI), with over 275 million cases annually. TV has been shown to secrete extracellular vesicles (TV-EVs) to regulate intercellular communication between parasites and host immune response; however, the mechanisms by innate immunity against TV-EVs are largely unknown. Herein, we aim to investigate the molecular mechanisms of inflammation induced by TV-EVs and identify novel proteins modulating the immune response in host cells. Firstly, the morphological characteristics of TV-EVs have been analyzed by transmission electron microscope (TEM) and nanoparticle tracking analysis, revealing that the vesicles are round-shaped bilayer membrane structures with size mostly about 100-120 nm. Additionally, the internalization of TV-EVs by host cells has been validated through immunofluorescence and TEM analysis. The multiplex immunoassay identified that TV-EVs induce the secretion of inflammatory cytokines, including CXCL1, IL-6, IL-8 and MIP-1β in THP-1 macrophages and ectocervical cells (Ect). Mechanistically, TV-EVs induce TLR3 overexpression to activate the NF-κB/NLRP3 pathway in THP-1 macrophages. Additionally, TV-EVs activate the PI3K-mediated NF-κB, p38 MAPK and ERK pathways in Ect. Moreover, TV-EV-induced TLR3 overexpression positively regulates the PI3K and NF-κB pathways, while simultaneously suppressing the p38 MAPK and ERK pathways in Ect. Proteomic analysis identified that TV-EVs upregulate MICB and TRAF3IP2, which are also positively regulated by TLR3 and involved in TV-EV-induced inflammatory cascade. Altogether, this study significantly advances our understanding of the immunomodulatory roles of TV-EVs in host cells, paving the way for future treatment of trichomoniasis and TV-associated STIs. |
| format | Article |
| id | doaj-art-633f6d91375a4f4eaa900e86143c3832 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-633f6d91375a4f4eaa900e86143c38322025-08-20T02:40:18ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-06-01216e101321610.1371/journal.ppat.1013216Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells.Ching-Yun HuangShu-Fang ChiuLichieh Julie ChuYuan-Ming YehPo-Jung HuangKuo-Lun LanYu-Ling TsaiChing-Chun LiuChien-Fu F ChenWei-Ning LinKuo-Yang HuangTrichomonas vaginalis (TV) is a flagellated parasite that causes trichomoniasis, the most common non-viral sexually transmitted infection (STI), with over 275 million cases annually. TV has been shown to secrete extracellular vesicles (TV-EVs) to regulate intercellular communication between parasites and host immune response; however, the mechanisms by innate immunity against TV-EVs are largely unknown. Herein, we aim to investigate the molecular mechanisms of inflammation induced by TV-EVs and identify novel proteins modulating the immune response in host cells. Firstly, the morphological characteristics of TV-EVs have been analyzed by transmission electron microscope (TEM) and nanoparticle tracking analysis, revealing that the vesicles are round-shaped bilayer membrane structures with size mostly about 100-120 nm. Additionally, the internalization of TV-EVs by host cells has been validated through immunofluorescence and TEM analysis. The multiplex immunoassay identified that TV-EVs induce the secretion of inflammatory cytokines, including CXCL1, IL-6, IL-8 and MIP-1β in THP-1 macrophages and ectocervical cells (Ect). Mechanistically, TV-EVs induce TLR3 overexpression to activate the NF-κB/NLRP3 pathway in THP-1 macrophages. Additionally, TV-EVs activate the PI3K-mediated NF-κB, p38 MAPK and ERK pathways in Ect. Moreover, TV-EV-induced TLR3 overexpression positively regulates the PI3K and NF-κB pathways, while simultaneously suppressing the p38 MAPK and ERK pathways in Ect. Proteomic analysis identified that TV-EVs upregulate MICB and TRAF3IP2, which are also positively regulated by TLR3 and involved in TV-EV-induced inflammatory cascade. Altogether, this study significantly advances our understanding of the immunomodulatory roles of TV-EVs in host cells, paving the way for future treatment of trichomoniasis and TV-associated STIs.https://doi.org/10.1371/journal.ppat.1013216 |
| spellingShingle | Ching-Yun Huang Shu-Fang Chiu Lichieh Julie Chu Yuan-Ming Yeh Po-Jung Huang Kuo-Lun Lan Yu-Ling Tsai Ching-Chun Liu Chien-Fu F Chen Wei-Ning Lin Kuo-Yang Huang Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. PLoS Pathogens |
| title | Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. |
| title_full | Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. |
| title_fullStr | Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. |
| title_full_unstemmed | Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. |
| title_short | Trichomonas vaginalis extracellular vesicles activate the NLRP3 inflammasome and TLR3-mediated inflammatory cascades in host cells. |
| title_sort | trichomonas vaginalis extracellular vesicles activate the nlrp3 inflammasome and tlr3 mediated inflammatory cascades in host cells |
| url | https://doi.org/10.1371/journal.ppat.1013216 |
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