Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease
Bustamante, Jacinta ; Arias, Andres A. ; Vogt, Guillaume ; Picard, Capucine ; Galicia, Lizbeth Blancas ; Prando, Carolina ; Grant, Audrey V. ; Marchal, Christophe C. ; Hubeau, Marjorie ; Chapgier, Ariane ... show 10 more
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Authors
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
Janniere, Lucile
Besse, Celine
Boland, Anne
Brisseau, Jean-Marie
Blanche, Stephane
Lortholary, Olivier
Fieschi, Claire
Emile, Jean-Francois
Boisson-Dupuis, Stephanie
Al-Muhsen, Saleh
Woda, Bruce A.
Newburger, Peter E.
Condino-Neto, Antonio
Dinauer, Mary C.
Abel, Laurent
Casanova, Jean-Laurent
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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.
Source
Nat Immunol. 2011 Mar;12(3):213-21. Epub 2011 Jan 30. Link to article on publisher's website