Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

ABSTRACT: Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This 'experiment of nature' indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria.

• Autores: Arias Sierra, Andrés Augusto; Bustamante, Jacinta; Vogt, Guillaume; Picard, Capucine; Blancas Galicia, Lizbeth; Prando Andrade, Carolina; Virginia Grant, Audrey; Marchal, Christophe C; Hubeau, Marjorie; Chapgier, Ariane; de Beaucoudrey, Ludovic; Puel, Anne; Feinberg, Jacqueline; Valinetz, Ethan; Jannière, Lucile; Besse, Céline; Boland, Anne; Brisseau, Jean Marie; Blanche, Stéphane; Lortholary, Olivier; Fieschi, Claire; Emile, Jean François; Boisson Dupuis, Stéphanie; Al-Muhsen, Saleh; Woda, Bruce; Newburger, Peter E.; Condino Neto, Antonio; Dinauer, Mary C.; Abel, Laurent; Casanova, Jean Laurent
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2011
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/36591
• Acceso en línea: https://hdl.handle.net/10495/36591
• Palabra clave: Células CHO; CHO Cells; Cricetinae; Tuberculosis Ganglionar; Tuberculosis, Lymph Node; Genes Ligados a X; Genes, X-Linked; Macrófagos; Macrophages; Glicoproteínas de Membrana; Membrane Glycoproteins; NADPH Oxidasa 2; NADPH Oxidase 2; Tuberculosis
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/