Vaccination against helminth IL-33 modulators permits immune-mediated parasite ejection.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-15 DOI:10.1016/j.celrep.2025.115721

Danielle J Smyth, Suzanne H Hodge, Nicole W P Ong, Josh Richards, Florent Colomb, Samuele Di Carmine, Vivien Shek, Tania Frangova, Marta Campillo Poveda, Rick M Maizels, Henry J McSorley

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引用次数: 0

Abstract

The murine intestinal nematode Heligmosomoides polygyrus bakeri (Hpb) modulates the host immune response via the Hpb alarmin release inhibitor (HpARI) family (HpARI1/2/3), which acts on interleukin (IL)-33, and the Hpb binds alarmin receptor and inhibits (HpBARI) family (HpBARI and HpBARI_Hom2), which acts on the IL-33 receptor ST2. Here, we find that this immunomodulation is evident only in the first week of infection and affects local and distal tissues. Vaccination with HpARI or HpBARI proteins raises antibody responses that block their immunomodulatory activities: HpARI2 vaccination results in significantly increased type 2 innate lymphoid cells (ILC2s), T helper (Th)2, and serum IL-4 and IL-5 responses, while HpBARI + HpBARI_Hom2 vaccination reverses infection-mediated ST2 suppression and increases Th2 immunity. A cocktail of HpARI2 + HpBARI + HpBARI_Hom2 gives robust protection against infection, associated with stunting of adult parasites, reduced egg burden, increased type 2 immune responses, and intestinal goblet cell expansion. Therefore, vaccination with immunomodulatory proteins can protect the host against infection and can be used as a tool for blocking the effects of specific parasite-derived proteins.

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针对蠕虫IL-33调节剂的疫苗接种允许免疫介导的寄生虫喷射。

小鼠肠道线虫（Hpb）通过作用于白细胞介素(IL)-33的Hpb报警蛋白释放抑制剂（HpARI）家族（HpARI1/2/3）和作用于IL-33受体ST2的HpBARI结合报警蛋白受体并抑制（HpBARI）家族（HpBARI和hppbari_hom2）调节宿主免疫应答。在这里，我们发现这种免疫调节仅在感染的第一周明显，并影响局部和远端组织。接种HpARI或HpBARI蛋白可提高抗体反应，阻断其免疫调节活性：hparii疫苗可显著提高2型先天淋巴样细胞（ILC2s）、辅助性T (Th)2和血清IL-4和IL-5反应，而HpBARI + hpbarari_hom2疫苗可逆转感染介导的ST2抑制并增强Th2免疫。HpARI2 + HpBARI + hpparari_hom2的混合物具有强大的抗感染保护作用，与成年寄生虫发育迟缓、卵负担减轻、2型免疫反应增强和肠杯状细胞扩增有关。因此，接种免疫调节蛋白可以保护宿主免受感染，并可作为阻断特定寄生虫来源蛋白作用的工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.