IL33 protects from recurrent C. difficile infection by restoration of humoral immunity.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Farha Naz, Md Jashim Uddin, Nicholas M Hagspiel, Mary K Young, David Tyus, Rachel Boone, Audrey C Brown, Girija Ramakrishnan, Isaura Rigo, Claire Fleming, Gregory R Madden, William A Petri
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引用次数: 0

Abstract

Clostridioides difficile infection (CDI) recurs in one of five patients. Monoclonal antibodies targeting the virulence factor TcdB reduce disease recurrence, suggesting that an inadequate anti-TcdB response to CDI leads to recurrence. In patients with CDI, we discovered that IL33 measured at diagnosis predicts future recurrence, leading us to test the role of IL33 signaling in the induction of humoral immunity during CDI. Using a mouse recurrence model, IL33 was demonstrated to be integral for anti-TcdB antibody production. IL33 acted via ST2+ ILC2 cells, facilitating germinal center T follicular helper (GC-Tfh) cell generation of antibodies. IL33 protection from reinfection was antibody-dependent, as mMT KO mice and mice treated with anti-CD20 mAb were not protected. These findings demonstrate the critical role of IL33 in generating humoral immunity to prevent recurrent CDI.

艰难梭菌感染(CDI)在五分之一的患者中会复发。针对毒力因子TcdB的单克隆抗体能减少疾病复发,这表明抗TcdB反应不足会导致CDI复发。在 CDI 患者中,我们发现诊断时测得的 IL33 可预测未来的复发,这促使我们检验 IL33 信号在 CDI 期间诱导体液免疫中的作用。通过使用小鼠复发模型,IL33 被证明是产生抗 TcdB 抗体不可或缺的因素。IL33通过ST2+ ILC2细胞发挥作用,促进生殖中心T滤泡辅助细胞(GC-Tfh)产生抗体。IL33对再感染的保护是抗体依赖性的,因为mMT KO小鼠和接受抗CD20 mAb治疗的小鼠没有保护作用。这些发现证明了IL33在产生体液免疫以预防复发性CDI中的关键作用。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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