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钩虫治疗可诱导抑制性调节性 T 细胞减少,伴随 Th2 炎症反应。

Hookworm treatment induces a decrease of suppressive regulatory T cell associated with a Th2 inflammatory response.

机构信息

Laboratory of Translational Research, ULB223, CHU Brugmann, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Clinic of Immunoallergology, CHU Brugmann, ULB, Brussels, Belgium.

出版信息

PLoS One. 2021 Jun 10;16(6):e0252921. doi: 10.1371/journal.pone.0252921. eCollection 2021.

Abstract

BACKGROUND

Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment.

METHODOLOGY

Twenty hookworm infected (HW+) and 14 non-infected subjects HW-from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1β, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFβ.

RESULTS

HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased.

CONCLUSION

During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.

摘要

背景

像其他寄生虫一样,钩虫(HW)会诱导一种调节性免疫反应,能够调节和抑制宿主对抗原的反应性。目前尚无关于治疗后免疫反应演变的数据。我们旨在表型化自然 HW 感染期间的调节性免疫反应及其治疗后的演变。

方法

我们纳入了 20 名钩虫感染(HW+)和 14 名非感染(HW-)的来自胡志明市周边地区的受试者。在使用阿苯达唑 400mg 治疗前、治疗后 2 周和 4 周采集了血液和粪便样本。HW+组还在治疗后 3 个月和 12 个月采集了额外的样本。测量了血液学参数、调节性 T 细胞(CD4+CD25hiFoxP3hi)和表面分子(CD39、CD62L、ICOS、PD-1、CD45RA)以及炎症和淋巴细胞分化细胞因子,如 IL-1β、IL-6、IFNγ、IL-4、IL-17、IL-10、IL-2 和 TGFβ。

结果

HW+受试者表现出更高的 Treg、TregICOS+、Treg PD1-、TregCD62L+和 CD45RA+FoxP3lo 静息调节性 T 细胞(rTreg)。CD45RA-FoxP3lo 非抑制性调节性 T 细胞也增加了。两组之间未观察到优先的 Th1/Th2 倾向,也未观察到 IL-10 的差异。治疗后,Treg、TregICOS+、TregCD62L+、Treg PD1-和 rTreg 减少,而 IL-4 和 IL-6 细胞因子增加。

结论

在 HW 感染期间,Treg 增加,并表现出异质性群体:一种高度抑制性和非抑制性 T 细胞表型。治疗后,具有免疫抑制表型的 Treg 与炎症性 Th2 反应平行减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1676/8191899/e6771363565b/pone.0252921.g001.jpg

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