TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection
BackgroundAlveolar echinococcosis (AE), a severe zoonotic disease predominantly endemic to pastoral regions, is characterized by hepatic parasitic lesions caused by Echinococcus multilocularis.MethodsThis study investigated the role of T-cell immunoglobulin and mucin domain-4 (TIMD4/Tim-4) in patien...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1600686/full |
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| author | Liang Wang Liang Wang Yumei Liu Yuyu Ma Xuan Zhou Xuan Zhou Maidinaimu Aibibula Xue Zhang Hui Zhao Jinping Zhou Fengming Tian Fengming Tian Xiumin Ma |
| author_facet | Liang Wang Liang Wang Yumei Liu Yuyu Ma Xuan Zhou Xuan Zhou Maidinaimu Aibibula Xue Zhang Hui Zhao Jinping Zhou Fengming Tian Fengming Tian Xiumin Ma |
| author_sort | Liang Wang |
| collection | DOAJ |
| description | BackgroundAlveolar echinococcosis (AE), a severe zoonotic disease predominantly endemic to pastoral regions, is characterized by hepatic parasitic lesions caused by Echinococcus multilocularis.MethodsThis study investigated the role of T-cell immunoglobulin and mucin domain-4 (TIMD4/Tim-4) in patients with hepatic AE. In total, 129 patients were enrolled from the First Affiliated Hospital of Xinjiang Medical University between 1 March 2018 and 1 March 2021. Histological, genetic, and serological tests were employed to evaluate Tim-4 and inflammatory cytokine expression. The liver immune microenvironment at the middle and late stages of mice infected with E. multilocularis was established in vitro to assess cytokine dynamics and liver fibrosis biomarkers.ResultsClinical analysis revealed the upregulation of Tim-4 within the hepatic lesions of patients with AE, with its expression spatially localized to macrophage-enriched regions and functionally linked to extracellular inflammatory modulation. Meanwhile, the liver tissues of the patients had characteristic pathological changes in the vesicles and progressive fibrotic remodeling, concurrent with a significant suppression of proinflammatory cytokine activity. Tim-4+ macrophages inhibited the release of proinflammatory cytokines at the middle and late stages of E. multilocularis infection to maintain immune tolerance, and inhibition of Tim-4 expression may even reverse the level of liver fibrosis in vitro.ConclusionsTim-4 attenuated the predominant proinflammatory response, thereby facilitating immune evasion by E. multilocularis. Notably, inhibition of Tim-4 in macrophages not only restored the inflammatory balance but also significantly reversed hepatic fibrotic progression. |
| format | Article |
| id | doaj-art-2f84fc4576c8446c97fa08ceee5690d7 |
| institution | OA Journals |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-2f84fc4576c8446c97fa08ceee5690d72025-08-20T02:35:51ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-06-011510.3389/fcimb.2025.16006861600686TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infectionLiang Wang0Liang Wang1Yumei Liu2Yuyu Ma3Xuan Zhou4Xuan Zhou5Maidinaimu Aibibula6Xue Zhang7Hui Zhao8Jinping Zhou9Fengming Tian10Fengming Tian11Xiumin Ma12Institute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaClinical Laboratory Center, Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaClinical Laboratory Center, Hospital of Traditional Chinese Medicine affiliated to Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaPostdoctoral Research Workstation of Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaInstitute of Medical Sciences of Xinjiang Medical University, Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, ChinaBackgroundAlveolar echinococcosis (AE), a severe zoonotic disease predominantly endemic to pastoral regions, is characterized by hepatic parasitic lesions caused by Echinococcus multilocularis.MethodsThis study investigated the role of T-cell immunoglobulin and mucin domain-4 (TIMD4/Tim-4) in patients with hepatic AE. In total, 129 patients were enrolled from the First Affiliated Hospital of Xinjiang Medical University between 1 March 2018 and 1 March 2021. Histological, genetic, and serological tests were employed to evaluate Tim-4 and inflammatory cytokine expression. The liver immune microenvironment at the middle and late stages of mice infected with E. multilocularis was established in vitro to assess cytokine dynamics and liver fibrosis biomarkers.ResultsClinical analysis revealed the upregulation of Tim-4 within the hepatic lesions of patients with AE, with its expression spatially localized to macrophage-enriched regions and functionally linked to extracellular inflammatory modulation. Meanwhile, the liver tissues of the patients had characteristic pathological changes in the vesicles and progressive fibrotic remodeling, concurrent with a significant suppression of proinflammatory cytokine activity. Tim-4+ macrophages inhibited the release of proinflammatory cytokines at the middle and late stages of E. multilocularis infection to maintain immune tolerance, and inhibition of Tim-4 expression may even reverse the level of liver fibrosis in vitro.ConclusionsTim-4 attenuated the predominant proinflammatory response, thereby facilitating immune evasion by E. multilocularis. Notably, inhibition of Tim-4 in macrophages not only restored the inflammatory balance but also significantly reversed hepatic fibrotic progression.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1600686/fullEchinococcus multilocularisTim-4parasite infectionimmunitymacrophageliver fibrosis |
| spellingShingle | Liang Wang Liang Wang Yumei Liu Yuyu Ma Xuan Zhou Xuan Zhou Maidinaimu Aibibula Xue Zhang Hui Zhao Jinping Zhou Fengming Tian Fengming Tian Xiumin Ma TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection Frontiers in Cellular and Infection Microbiology Echinococcus multilocularis Tim-4 parasite infection immunity macrophage liver fibrosis |
| title | TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| title_full | TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| title_fullStr | TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| title_full_unstemmed | TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| title_short | TIM4+macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| title_sort | tim4 macrophages suppress the proinflammatory response to maintain the chronic alveolar echinococcosis infection |
| topic | Echinococcus multilocularis Tim-4 parasite infection immunity macrophage liver fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1600686/full |
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