دورية أكاديمية
A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection
| العنوان: | A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection |
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| المؤلفون: | De Trez, Carl, Stijlemans, Benoit, Bockstal, Viki, Cnops, Jennifer, Korf, Hannelie, Van Snick, Jacques, Caljon, Guy, Muraille, Eric, Humphreys, Ian R., Boon, Louis, Van Ginderachter, Jo A., Magez, Stefan |
| المصدر: | FRONTIERS IN IMMUNOLOGY ; ISSN: 1664-3224 |
| سنة النشر: | 2020 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Biology and Life Sciences, Medicine and Health Sciences, brucei, IL-10, inflammation, T cells, IL-27, Blimp-1, TRANSCRIPTIONAL REPRESSOR BLIMP-1, IFN-GAMMA, B-CELLS, AFRICAN TRYPANOSOMIASIS, INTERFERON-GAMMA, EXPRESSION, INFECTION, MICE, INTERLEUKIN-27, RESISTANCE |
| الوصف: | In many infectious diseases, the immune response operates as a double-edged sword. While required for protective immunity, infection-induced inflammation can be detrimental if it is not properly controlled, causing collateral body damage and potentially leading to death. It is in this context that the potent anti-inflammatory cytokine interleukin-10 (IL-10) is required to dampen the pro-inflammatory immune response that hallmarks trypanosomosis. Effective control of this infection requires not just the action of antibodies specific for the parasite's variable surface glycoprotein (VSG) coat antigens, but also a pro-inflammatory immune response mediated mainly by IFN gamma, TNF, and NO. However, strict control of inflammation is mandatory, as IL-10-deficient mice succumb from an unrestrained cytokine storm within 10 days of aTrypanosome bruceiinfection. The relevant cellular source of IL-10 and the associated molecular mechanisms implicated in its trypanosomosis associated production are poorly understood. Using an IL-10 reporter mouse strain (Vert-X), we demonstrate here that NK cells, CD8(+)T cells and CD4(+)T cells as well as B cells and plasma cells constitute potential cellular sources of IL-10 within the spleen and liver during acute infection. The IL-10 wave follows peak pro-inflammatory cytokine production, which accompanied the control of peak parasitemia. Similar results were observed following conventional experimental needle infection and physiological infections viaT. brucei-infected tsetse flies. Our results show that conditional T cell-specific ablation of the IL-10 regulatingPrdm1gene (encoding for the Blimp-1 transcription factor), leads to an uncontrolled trypanosome-induced pro-inflammatory syndrome like the one observed in infected IL-10-deficient mice. This result indicates that the biological role of IL-10-derived from non-T cells, including NK cells, is of minor importance when considering host survival. The cytokine IL-27 that is also considered to be an IL-10 regulator, did not affect ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/8671133Test; http://hdl.handle.net/1854/LU-8671133Test; http://dx.doi.org/10.3389/fimmu.2020.01085Test; https://biblio.ugent.be/publication/8671133/file/8671134Test |
| DOI: | 10.3389/fimmu.2020.01085 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2020.01085Test https://biblio.ugent.be/publication/8671133Test http://hdl.handle.net/1854/LU-8671133Test https://biblio.ugent.be/publication/8671133/file/8671134Test |
| حقوق: | Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CAA2E61 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2020.01085 |
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