法国巴黎西岱大学Jacinta Bustamante等研究人员合作发现，人类IRF1控制巨噬细胞对分枝杆菌的IFN-γ免疫。相关论文于2023年2月2日发表于国际学术期刊《细胞》杂志上。
研究人员报道了与遗传完整IRF1缺陷无关的儿童，以及由弱毒分枝杆菌和相关巨噬内病原体引导的早期发作、多重且危及生命的疾病。这些儿童没有严重的病毒性疾病史，尽管他们接触过许多病毒，包括SARS-CoV-2，这种病毒对干扰素-α/β免疫受损的个体来说是危及生命的。在体外刺激的白细胞或成纤维细胞中，IRF1对IFN-γ的依赖反应在定量和定性上都比IFN-α/β强得多。此外，IFR1缺陷的单核吞噬细胞在受到IFN-γ刺激时不能正常控制分枝杆菌和相关病原体。相比之下，在IRF1缺陷的成纤维细胞中，对包括SARS-CoV-2在内的9种病毒的IFN-α/β依赖的内在免疫几乎正常。人类IRF1对于IFN-γ依赖的巨噬细胞对分枝杆菌的免疫至关重要，但对于IFN-α/β依赖的抗病毒免疫基本上是多余的。
据了解，人类IFN-γ依赖性巨噬细胞免疫的先天性错误是分枝杆菌疾病的基础，而IFN-α/β依赖性固有免疫的先天性错误是病毒性疾病的基础。两种类型的IFN都诱导转录因子IRF1。
附：英文原文
Title: Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria
Author: Jérémie Rosain, Anna-Lena Neehus, Jérémy Manry, Rui Yang, Jérémie Le Pen, Wassim Daher, Zhiyong Liu, Yi-Hao Chan, Natalia Tahuil, zden Türel, Mathieu Bourgey, Masato Ogishi, Jean-Marc Doisne, Helena M. Izquierdo, Takayoshi Shirasaki, Tom Le Voyer, Antoine Guérin, Paul Bastard, Marcela Moncada-Vélez, Ji Eun Han, Taushif Khan, Franck Rapaport, Seon-Hui Hong, Andrew Cheung, Kathrin Haake, Barbara C. Mindt, Laura Pérez, Quentin Philippot, Danyel Lee, Peng Zhang, Darawan Rinchai, Fatima Al Ali, Manar Mahmoud Ahmad Ata, Mahbuba Rahman, Jessica N. Peel, Sren Heissel, Henrik Molina, Yasemin Kendir-Demirkol, Rasheed Bailey, Shuxiang Zhao, Jonathan Bohlen, Mathieu Mancini, Yoann Seeleuthner, Marie Roelens, Lazaro Lorenzo, Camille Soudée, María Elvira Josefina Paz, María Laura González, Mohamed Jeljeli, Jean Soulier, Serge Romana, Anne-Sophie L’Honneur, Marie Materna, Rubén Martínez-Barricarte, Mathieu Pochon, Carmen Oleaga-Quintas, Alexandre Michev, Mélanie Migaud
Issue&Volume: 2023/02/02
Abstract: Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
DOI: 10.1016/j.cell.2022.12.038
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01581-1