Tuberculosis in otherwise healthy adults with inherited TNF deficiency

• 成果类型: Article
• 署名作者: Arias, Andres A.; Neehus, Anna-Lena; Ogishi, Masato; Meynier, Vincent; Krebs, Adam; Lazarov, Tomi; Lee, Angela M.; Arango-Franco, Carlos A.; Yang, Rui; Orrego, Julio; Corcini Berndt, Melissa; Rojas, Julian; Li, Hailun; Rinchai, Darawan; Erazo-Borras, Lucia; Han, Ji Eun; Pillay, Bethany; Ponsin, Khoren; Chaldebas, Matthieu; Philippot, Quentin; Bohlen, Jonathan; Rosain, Jeremie; Le Voyer, Tom; Janotte, Till; Amarajeeva, Krishnajina; Soudee, Camille; Brollo, Marion; Wiegmann, Katja; Marquant, Quentin; Seeleuthner, Yoann; Lee, Danyel; Laine, Candice; Kloos, Doreen; Bailey, Rasheed; Bastard, Paul; Keating, Narelle; Rapaport, Franck; Khan, Taushif; Moncada-Velez, Marcela; Camila Carmona, Maria; Obando, Catalina; Alvarez, Jesus; Carlos Catano, Juan; Martinez-Rosado, Larry Luber; Sanchez, Juan P.; Tejada-Giraldo, Manuela; L'Honneur, Anne-Sophie; Agudelo, Maria L.; Perez-Zapata, Lizet J.; Arboleda, Diana M.; Fernando Alzate, Juan; Cabarcas, Felipe; Zuluaga, Alejandra; Pelham, Simon J.; Ensser, Armin; Schmidt, Monika; Velasquez-Lopera, Margarita M.; Jouanguy, Emmanuelle; Puel, Anne; Kronke, Martin; Ghirardello, Stefano; Borghesi, Alessandro; Pahari, Susanta; Boisson, Bertrand; Pittaluga, Stefania; Ma, Cindy S.; Emile, Jean-Francois; Notarangelo, Luigi D.; Tangye, Stuart G.; Marr, Nico; Lachmann, Nico; Salvator, Helene; Schlesinger, Larry S.; Zhang, Peng; Glickman, Michael S.; Nathan, Carl F.; Geissmann, Frederic; Abel, Laurent; Luis Franco, Jose; Bustamante, Jacinta; Casanova, Jean-Laurent; Boisson-Dupuis, Stephanie
• 署名单位: Universidad de Antioquia; Universidad de Antioquia; Rockefeller University; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Garvan Institute of Medical Research; University of New South Wales Sydney; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; INRAE; Universite Paris Saclay; University of Cologne; University of Cologne; Hannover Medical School; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Walter & Eliza Hall Institute; University of Melbourne; Jackson Laboratory; Universidad de Antioquia; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Cochin - APHP; Universidad de Antioquia; Universidad de Antioquia; University of Erlangen Nuremberg; Universidad de Antioquia; University of Cologne; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Texas Biomedical Research Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Ambroise-Pare - APHP; National Institutes of Health (NIH) - USA; Division of Intramural Research (DIR); NIH National Institute of Allergy & Infectious Diseases (NIAID); Sidra Medical & Research Center; Qatar Foundation (QF); Hamad Bin Khalifa University-Qatar; Hannover Medical School; Hospital Foch; Universite Paris Saclay; Howard Hughes Medical Institute; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6244
• DOI: 10.1038/s41586-024-07866-3
• 发表日期: 2024-09-05
• 页码: 417-+
• 关键词: tumor-necrosis-factor; chronic granulomatous-disease; factor-alpha; macrophages; infection; immunity; mice; chemokines

摘要

Severe defects in human IFN gamma immunity predispose individuals to both Bacillus Calmette-Guerin disease and tuberculosis, whereas milder defects predispose only to tuberculosis(1). Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFN gamma. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells(2) from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guerin disease and tuberculosis(3). Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.