树突状细胞介导的对隐孢子虫分泌效应因子的反应可促进寄生虫特异性 CD8+ T 细胞反应

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-06-01 DOI:10.1016/j.mucimm.2024.03.003
Breanne E. Haskins , Jodi A. Gullicksrud , Bethan A. Wallbank , Jennifer E. Dumaine , Amandine Guérin , Ian S. Cohn , Keenan M. O'Dea , Ryan D. Pardy , Maria I. Merolle , Lindsey A. Shallberg , Emma N. Hunter , Jessica H. Byerly , Eleanor J. Smith , Gracyn Y. Buenconsejo , Briana I. McLeod , David A. Christian , Boris Striepen , Christopher A. Hunter
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引用次数: 0

摘要

然而,了解这种感染如何产生 T 细胞反应以及它们如何介导寄生虫控制一直是个挑战。在这里,我们设计表达了一种寄生虫效应蛋白(MEDLE-2),它含有 MHC-I 限制性 SIINFEKL 表位,可被 TCR 转基因 OT-I CD8 T 细胞识别。这些改造过的寄生虫诱导了内源性 SIINFEKL 特异性和 OT-I CD8 T 细胞的扩增,这些 T 细胞是 IFN-γ 的来源,可以限制 SIINFEKL 的生长。 这种 T 细胞反应依赖于效应物的易位,在另一种分泌型寄生虫效应物(ROP1)上也观察到了类似的结果。虽然感染和这些转位效应蛋白仅限于肠上皮细胞(IEC),但需要 I 型树突状细胞(cDC1)才能产生 CD8 T 细胞对这些模型抗原的反应。这些数据集强调了效应蛋白是免疫系统的潜在靶标,并表明肠细胞和 cDC1 之间的串联对于 CD8 T 细胞对......的应答至关重要。
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Dendritic cell-mediated responses to secreted Cryptosporidium effectors promote parasite-specific CD8+ T cell responses

Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here, Cryptosporidium was engineered to express a parasite effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by T cell receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8+ T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8+ T cells that were a source of interferon-gamma (IFN-γ) that could restrict growth of Cryptosporidium. This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (rhoptry protein 1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells, type 1 conventional dendritic cells were required to generate CD8+ T cell responses to these model antigens. These data sets highlight Cryptosporidium effectors as potential targets of the immune system and suggest that crosstalk between enterocytes and type 1 conventional dendritic cells is crucial for CD8+ T cell responses to Cryptosporidium.

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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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