 Tuberculosis in otherwise healthy adults with inherited TNF deficiencyAndrés A. Arias,
Anna-Lena Neehus (),
Masato Ogishi,
Vincent Meynier,
Adam Krebs,
Tomi Lazarov,
Angela M. Lee,
Carlos A. Arango-Franco,
Rui Yang,
Julio Orrego,
Melissa Corcini Berndt,
Julian Rojas,
Hailun Li,
Darawan Rinchai,
Lucia Erazo-Borrás,
Ji Eun Han,
Bethany Pillay,
Khoren Ponsin,
Matthieu Chaldebas,
Quentin Philippot,
Jonathan Bohlen,
Jérémie Rosain,
Tom Voyer,
Till Janotte,
Krishnajina Amarajeeva,
Camille Soudée,
Marion Brollo,
Katja Wiegmann,
Quentin Marquant,
Yoann Seeleuthner,
Danyel Lee,
Candice Lainé,
Doreen Kloos,
Rasheed Bailey,
Paul Bastard,
Narelle Keating,
Franck Rapaport,
Taushif Khan,
Marcela Moncada-Vélez,
María Camila Carmona,
Catalina Obando,
Jesús Alvarez,
Juan Carlos Cataño,
Larry Luber Martínez-Rosado,
Juan P. Sanchez,
Manuela Tejada-Giraldo,
Anne-Sophie L’Honneur,
María L. Agudelo,
Lizet J. Perez-Zapata,
Diana M. Arboleda,
Juan Fernando Alzate,
Felipe Cabarcas,
Alejandra Zuluaga,
Simon J. Pelham,
Armin Ensser,
Monika Schmidt,
Margarita M. Velásquez-Lopera,
Emmanuelle Jouanguy,
Anne Puel,
Martin Krönke,
Stefano Ghirardello,
Alessandro Borghesi,
Susanta Pahari,
Bertrand Boisson,
Stefania Pittaluga,
Cindy S. Ma,
Jean-François Emile,
Luigi D. Notarangelo,
Stuart G. Tangye,
Nico Marr,
Nico Lachmann,
Hélène Salvator,
Larry S. Schlesinger,
Peng Zhang,
Michael S. Glickman,
Carl F. Nathan,
Frédéric Geissmann,
Laurent Abel,
José Luis Franco (),
Jacinta Bustamante,
Jean-Laurent Casanova () and
Stéphanie Boisson-Dupuis
Nature, 2024, vol. 633, issue 8029, 417-425 Abstract: Abstract Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette–Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. 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 IFNγ. 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) cells2 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–Guérin disease and tuberculosis3. 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. Date: 2024 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:633:y:2024:i:8029:d:10.1038_s41586-024-07866-3 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-024-07866-3 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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