Details

Autor(en) / Beteiligte

• Bustamante, Jacinta
• Arias, Andres A
• Vogt, Guillaume
• Picard, Capucine
• Galicia, Lizbeth Blancas
• Prando, Carolina
• Grant, Audrey V
• 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

Titel

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

Ist Teil von

• Nature immunology, 2011-03, Vol.12 (3), p.213

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.