Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment

被引：17

作者：

Yasen, Aimaiti ^{[1
]}

Sun, Wujianan ^{[4
]}

Aini, Abudusalamu ^{[1
]}

Aji, Tuerganaili ^{[2
]}

Shao, Yingmei ^{[2
]}

Wang, Hui ^{[3
]}

Li, Kun ^{[4
]}

Li, Wending ^{[1
]}

Zhang, Chuanshan ^{[3
]}

Ahan, Ayifuhan ^{[2
]}

Jiang, Tiemin ^{[2
]}

Wang, Zongding ^{[1
]}

Zhang, Wenbao ^{[1
]}

Sun, Cheng ^{[5
]}

Qu, Kun ^{[4
,5
]}

Wen, Hao ^{[1
,2
]}

机构：

[1] Xinjiang Med Univ, State Key Lab Pathogenesis Prevent & Management H, Affiliated Hosp 1, Urumqi, Peoples R China

[2] Xinjiang Med Univ, Digest & Vasc Surg Ctr, Dept Hepatobiliary & Echinococcosis Surg, Affiliated Hosp 1, Urumqi, Peoples R China

[3] Xinjiang Med Univ, Clin Med Inst, Xinjiang Uyghur Autonomous Reg Key Lab Echinococc, Affiliated Hosp 1, Urumqi, Peoples R China

[4] Univ Sci & Technol China, Dept Oncol, Affiliated Hosp 1,Sch Basic Med Sci,Div Life Sci, UST,Div Mol Med,Hefei Natl Lab Phys Sci Microscal, Hefei, Peoples R China

[5] Univ Sci & Technol China, Sch Data Sci, Hefei, Peoples R China

来源：

INFECTION AND IMMUNITY | 2021年 / 89卷 / 12期

基金：

中国国家自然科学基金;

关键词：

hepatic cystic echinococcosis; lesion microenvironment; immune cells; heterogeneity; single-cell sequencing;

D O I：

10.1128/IAI.00297-21

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4(+) T cell populations were found, and there were more regulatory-CD4(+) T cells (Treg-CD4(+)) and Th2-CD4(+) T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4(+) T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.

引用

页数：5

共 58 条

[1]

Hao W, Vuitton L, Tuxun T, Jun L, Vuitton DA, Zhang WB, McManus DP., Echinococcosis in the 21st century, Clin Microbiol Rev, 32, pp. e0005-e0018, (2019)

[2]

Budke CM, Carabin H, Ndimubanzi PC, Nguyen H, Rainwater E, Dickey M, Bhattarai R, Oleksandr Zeziulin O, Qian MB., A systematic review of the literature on cystic echinococcosis frequency worldwide and its associated clinical manifestations, Am J Trop Med Hyg, 88, pp. 1011-1027, (2013)

[3]

Budke CM, Deplazes P, Torgerson PR., Global socioeconomic impact of cystic echinococcosis, Emerg Infect Dis, 12, pp. 296-303, (2006)

[4]

Tamarozzi F, Akhan O, Cretu CM, Vutova K, Akinci D, Chipeva R, Ciftci T, Constantin CM, Fabiani M, Golemanov B, Janta D, Mihailescu P, Muhtarov M, Orsten S, Petrutescu M, Pezzotti P, Popa AC, Popa LG, Popa MI, Velev V, Siles-Lucas M, Brunetti E, Casulli A., Prevalence of abdominal cystic echinococcosis in rural Bulgaria, Romania, and Turkey: a cross-sectional, ultrasound-based, population study from the HERACLES project, Lancet Infect Dis, 18, pp. 769-778, (2018)

[5]

McManus DP, Gray DJ, Zhang W, Yang Y., Diagnosis, treatment, and management of echinococcosis, BMJ, 344, (2012)

[6]

Brunetti E, Kern P, Vuitton DA, Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans, Acta Trop, 114, pp. 1-16, (2010)

[7]

Junghanss T, da Silva AM, Horton J, Chiodini PL, Brunetti E., Clinical management of cystic echinococcosis: state of the art, problems, and perspectives, Am J Trop Med Hyg, 79, pp. 301-311, (2008)

[8]

Gottstein B, Soboslay P, Ortona E, Wang J, Siracusano A, Vuitton DA., Immunology of alveolar and cystic echinococcosis (AE and CE), Adv Parasitol, 96, pp. 1-54, (2017)

[9]

Vuitton DA., The ambiguous role of immunity in echinococcosis: protection of the host or of the parasite?, Acta Trop, 85, pp. 119-132, (2003)

[10]

Pan W, Zhou H-J, Shen YJ, Wang Y, Xu YX, Hu Y, Jiang YY, Yuan ZY, Ugwu CE, Cao JP., Surveillance on the status of immune cells after Echinococcus granulosus protoscoleces infection in Balb/C mice, PLoS One, 8, (2013)

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