Tuberculosis in otherwise healthy adults with inherited TNF deficiency Journal Article
| Authors: | Arias, A. A.; Neehus, A. L.; Ogishi, M.; Meynier, V.; Krebs, A.; Lazarov, T.; Lee, A. M.; Arango-Franco, C. A.; Yang, R.; Orrego, J.; Corcini Berndt, M.; Rojas, J.; Li, H.; Rinchai, D.; Erazo-Borrás, L.; Han, J. E.; Pillay, B.; Ponsin, K.; Chaldebas, M.; Philippot, Q.; Bohlen, J.; Rosain, J.; Le Voyer, T.; Janotte, T.; Amarajeeva, K.; Soudée, C.; Brollo, M.; Wiegmann, K.; Marquant, Q.; Seeleuthner, Y.; Lee, D.; Lainé, C.; Kloos, D.; Bailey, R.; Bastard, P.; Keating, N.; Rapaport, F.; Khan, T.; Moncada-Vélez, M.; Carmona, M. C.; Obando, C.; Alvarez, J.; Cataño, J. C.; Martínez-Rosado, L. L.; Sanchez, J. P.; Tejada-Giraldo, M.; L’Honneur, A. S.; Agudelo, M. L.; Perez-Zapata, L. J.; Arboleda, D. M.; Alzate, J. F.; Cabarcas, F.; Zuluaga, A.; Pelham, S. J.; Ensser, A.; Schmidt, M.; Velásquez-Lopera, M. M.; Jouanguy, E.; Puel, A.; Krönke, M.; Ghirardello, S.; Borghesi, A.; Pahari, S.; Boisson, B.; Pittaluga, S.; Ma, C. S.; Emile, J. F.; Notarangelo, L. D.; Tangye, S. G.; Marr, N.; Lachmann, N.; Salvator, H.; Schlesinger, L. S.; Zhang, P.; Glickman, M. S.; Nathan, C. F.; Geissmann, F.; Abel, L.; Franco, J. L.; Bustamante, J.; Casanova, J. L.; Boisson-Dupuis, S. |
| Article Title: | Tuberculosis in otherwise healthy adults with inherited TNF deficiency |
| 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. © The Author(s) 2024. |
| Keywords: | immunohistochemistry; adult; controlled study; human cell; genetics; case report; interferon; flow cytometry; cd8+ t lymphocyte; tumor associated leukocyte; phenotype; cytology; metabolism; glycoprotein gp 100; interleukin 2; computer assisted tomography; prevalence; granulocyte macrophage colony stimulating factor; interleukin 10; tumor necrosis factor receptor 1; immunofluorescence; regulatory t lymphocyte; immunology; mycobacterium tuberculosis; genetic transfection; tumor necrosis factor-alpha; gamma interferon; microarray analysis; escherichia coli; antibody response; cd4+ t lymphocyte; western blotting; immunoprecipitation; homozygote; immunoblotting; reactive oxygen metabolite; natural killer cell; tumor immunity; cytokine production; innate immunity; pleura effusion; interleukin 17; immunity; interferon-gamma; monocyte; microbiology; macrophage; macrophages; cytokine release; homeostasis; site directed mutagenesis; rifampicin; thymectomy; lung biopsy; lobectomy; leukocytosis; t lymphocyte activation; interleukin 12; listeria monocytogenes; bacterium; tuberculosis; peripheral blood mononuclear cell; normal human; phagocyte; induced pluripotent stem cells; lung alveolus macrophage; macrophages, alveolar; tumor necrosis factor; rna sequence; respiratory failure; immunization; programmed death 1 ligand 1; lung lavage; cell; lymphoid cell; bcg vaccination; lung tuberculosis; granulocyte-macrophage colony-stimulating factor; principal component analysis; septic shock; tumor necrosis factor inhibitor; bronchoalveolar lavage fluid; cd40 antigen; seroconversion; receptors, tumor necrosis factor, type i; ethambutol; isoniazid; neutrophilia; pyrazinamide; coinfection; tuberculosis, pulmonary; induced pluripotent stem cell; sanger sequencing; humans; human; male; female; article; hek293 cell line; respiratory burst; whole exome sequencing; gene editing; tumor necrosis factor inhibitors; thymus tissue; disease spread |
| Journal Title: | Nature |
| Volume: | 633 |
| Issue: | 8029 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-12 |
| Start Page: | 417 |
| End Page: | 425 |
| Language: | English |
| DOI: | 10.1038/s41586-024-07866-3 |
| PUBMED: | 39198650 |
| PROVIDER: | scopus |
| PMCID: | PMC11390478 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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