Smyth Danielle J, Hodge Suzanne H, Ong Nicole W P, Richards Josh, Colomb Florent, Di Carmine Samuele, Shek Vivien, Frangova Tania, Poveda Marta Campillo, Maizels Rick M, McSorley Henry J
Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Centre for Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow G12 8TA, UK.
Cell Rep. 2025 May 27;44(5):115721. doi: 10.1016/j.celrep.2025.115721. Epub 2025 May 15.
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.
鼠肠道线虫巴氏多房棘球绦虫（Hpb）通过作用于白细胞介素（IL）-33的Hpb警报素释放抑制剂（HpARI）家族（HpARI1/2/3）以及作用于IL-33受体ST2的Hpb结合警报素受体并抑制（HpBARI）家族（HpBARI和HpBARI_Hom2）来调节宿主免疫反应。在此，我们发现这种免疫调节仅在感染的第一周明显，且影响局部和远端组织。用HpARI或HpBARI蛋白进行疫苗接种可引发抗体反应，从而阻断它们的免疫调节活性：接种HpARI2可导致2型天然淋巴细胞（ILC2s）、辅助性T（Th）2细胞以及血清IL-4和IL-5反应显著增加，而接种HpBARI + HpBARI_Hom2可逆转感染介导的ST2抑制并增强Th2免疫。HpARI2 + HpBARI + HpBARI_Hom2的组合能提供强大的抗感染保护，这与成虫发育迟缓、虫卵负荷减少、2型免疫反应增强以及肠道杯状细胞扩张有关。因此，用免疫调节蛋白进行疫苗接种可保护宿主免受感染，并可作为一种阻断特定寄生虫衍生蛋白作用的工具。
