IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps
Abstract The widespread prevalence of alveolar echinococcosis (AE) caused by Echinococcus multilocularis infection poses a significant threat to human health. E. multilocularis is found primarily in the Northern Hemisphere. Given the limitations of current treatment methods, primarily surgical resec...
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BMC
2025-07-01
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| Series: | Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s13567-025-01572-2 |
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| author | Haining Zhang Ru Meng Fan Zhang Ao Chen Hongrun Ge Wangkai Chen Zhi Li Yong Fu |
| author_facet | Haining Zhang Ru Meng Fan Zhang Ao Chen Hongrun Ge Wangkai Chen Zhi Li Yong Fu |
| author_sort | Haining Zhang |
| collection | DOAJ |
| description | Abstract The widespread prevalence of alveolar echinococcosis (AE) caused by Echinococcus multilocularis infection poses a significant threat to human health. E. multilocularis is found primarily in the Northern Hemisphere. Given the limitations of current treatment methods, primarily surgical resection, there is a pressing need for more effective therapeutic options. We established a mouse model of E. multilocularis infection by injecting E. multilocularis protoscoleces into C57BL/6 mice. The formation of neutrophil extracellular traps (NETs) following E. multilocularis infection was identified and validated using various techniques, including transcriptome sequencing, scanning electron microscopy (SEM) and flow cytometry. We found that the knockout of the Indoleamine 2, 3 dioxygenase 1 (IDO1) gene or the administration of IDO1 inhibitors resulted in a decrease in the levels of NET-related molecules, including CitH3, MPO, PAD4, PR3, NE, and MPO–DNA complexes, as well as cfDNA. In addition, after the addition of the IDO1 inhibitor, the levels of p65, phospho-p65, p50/105, and REL increased. These results showed that IDO1 promotes the formation of NETs and inhibits NF-κB activation. Moreover, IDO1 inhibits AE progression by regulating NET formation. In conclusion, this study revealed that IDO1 inhibits AE progression by regulating NET formation, and this regulation may be associated with IDO1-induced neutrophil production and NF-κB signalling activation. These results are valuable for understanding the pathogenesis of E. multilocularis and may offer new insights for the prevention and treatment of AE. |
| format | Article |
| id | doaj-art-6531f4db9b674e5a8284b6dccfb1c97c |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-6531f4db9b674e5a8284b6dccfb1c97c2025-08-20T04:01:35ZengBMCVeterinary Research1297-97162025-07-0156111110.1186/s13567-025-01572-2IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular trapsHaining Zhang0Ru Meng1Fan Zhang2Ao Chen3Hongrun Ge4Wangkai Chen5Zhi Li6Yong Fu7Academy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityXining Animal Disease Control CenterAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAcademy of Animal Sciences and Veterinary Medicine, Qinghai Provincial Key Laboratory of Pathogen Diagnosis for Animal Diseases and Green Technical Research for Prevention and Control, Qinghai UniversityAbstract The widespread prevalence of alveolar echinococcosis (AE) caused by Echinococcus multilocularis infection poses a significant threat to human health. E. multilocularis is found primarily in the Northern Hemisphere. Given the limitations of current treatment methods, primarily surgical resection, there is a pressing need for more effective therapeutic options. We established a mouse model of E. multilocularis infection by injecting E. multilocularis protoscoleces into C57BL/6 mice. The formation of neutrophil extracellular traps (NETs) following E. multilocularis infection was identified and validated using various techniques, including transcriptome sequencing, scanning electron microscopy (SEM) and flow cytometry. We found that the knockout of the Indoleamine 2, 3 dioxygenase 1 (IDO1) gene or the administration of IDO1 inhibitors resulted in a decrease in the levels of NET-related molecules, including CitH3, MPO, PAD4, PR3, NE, and MPO–DNA complexes, as well as cfDNA. In addition, after the addition of the IDO1 inhibitor, the levels of p65, phospho-p65, p50/105, and REL increased. These results showed that IDO1 promotes the formation of NETs and inhibits NF-κB activation. Moreover, IDO1 inhibits AE progression by regulating NET formation. In conclusion, this study revealed that IDO1 inhibits AE progression by regulating NET formation, and this regulation may be associated with IDO1-induced neutrophil production and NF-κB signalling activation. These results are valuable for understanding the pathogenesis of E. multilocularis and may offer new insights for the prevention and treatment of AE.https://doi.org/10.1186/s13567-025-01572-2Echinococcus multilocularisneutrophil extracellular trapsIDO1NF-κB |
| spellingShingle | Haining Zhang Ru Meng Fan Zhang Ao Chen Hongrun Ge Wangkai Chen Zhi Li Yong Fu IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps Veterinary Research Echinococcus multilocularis neutrophil extracellular traps IDO1 NF-κB |
| title | IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| title_full | IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| title_fullStr | IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| title_full_unstemmed | IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| title_short | IDO1 promotes Echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| title_sort | ido1 promotes echinococcus multilocularis infection by regulating the formation of neutrophil extracellular traps |
| topic | Echinococcus multilocularis neutrophil extracellular traps IDO1 NF-κB |
| url | https://doi.org/10.1186/s13567-025-01572-2 |
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