艾克斯-马赛大学Elena Tomasello小组取得一项新突破。他们的最新研究揭示了浆细胞样树突状细胞在小鼠全身或呼吸道病毒感染中是可有可无或有害的。2025年9月29日出版的《自然—免疫学》发表了这项成果。

为了克服这一问题，小组通过在pDCs中唯一共表达的Siglech和Pacsin1基因的协调控制下表达白喉毒素，设计了特异性和组成性缺乏pDCs的无pDC小鼠。无pDC小鼠对无主题巨细胞病毒全身感染具有保护性免疫，对流感病毒和SARS-CoV-2鼻内感染表现出更高的存活率和更少的肺部免疫病理。他们，与流行的教条相反，该课题组揭示了pDCs及其干扰素在几种病毒感染中是可有可无的或有害的。不含pDCs的小鼠将能够严格地重新评估pDCs在健康和疾病中的作用。

据悉，浆细胞样树突状细胞（pDCs）是I/III型干扰素的主要生产者。由于干扰素对抗病毒防御至关重要，人们认为pDCs在这一过程中起着至关重要的作用；然而，支持这一论断的有力证据很少。消除pDCs或破坏其干扰素产生的遗传或药理学操作通常会影响其他细胞，使解释混淆。

附：英文原文

Title: Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections

Author: Ngo, Clemence, Pierini-Malosse, Camille, Rahmani, Khalissa, Valente, Michael, Collinet, Nils, Bessou, Gilles, Guerry, Capucine, Fabregue, Manon, Mathieu, Solene, Sharkaoui, Sarah, Mazzoli, Sophie, Sansoni, Amandine, Fiore, Frederic, Laprie, Caroline, Alexopoulou, Lena, Gaya, Mauro, Gregoire, Claude, Broggi, Achille, Wurbel, Sarah, Rua, Rjane, Haidar, Narjess, Milpied, Pierre, Escalire, Bertrand, Vu Manh, Thien Phong, Fallet, Mathieu, Chasson, Lionel, Tran, Hien, Baranek, Thomas, Le Bert, Marc, Malissen, Bernard, Zarubica, Ana, Dalod, Marc, Tomasello, Elena

Issue&Volume: 2025-09-29

Abstract: Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.

DOI: 10.1038/s41590-025-02288-3

Source: https://www.nature.com/articles/s41590-025-02288-3