title: 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.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U980, Paris, France.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Andres A
authors.initials: AA
authors.lastname: Arias
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Lizbeth Blancas
authors.initials: LB
authors.lastname: Galicia
authors.forename: Carolina
authors.initials: C
authors.lastname: Prando
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Christophe C
authors.initials: CC
authors.lastname: Marchal
authors.forename: Marjorie
authors.initials: M
authors.lastname: Hubeau
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Ludovic
authors.initials: L
authors.lastname: de Beaucoudrey
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Ethan
authors.initials: E
authors.lastname: Valinetz
authors.forename: Lucile
authors.initials: L
authors.lastname: Jannière
authors.forename: Céline
authors.initials: C
authors.lastname: Besse
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Brisseau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Bruce
authors.initials: B
authors.lastname: Woda
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
authors.forename: Mary C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D050172:Genes, X-Linked; D020022:Genetic Predisposition to Disease; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics* / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases