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


Jacinta Bustamante, University of Paris René Descartes
Andres A. Arias, Institut National de la Santé et de la Recherche Médicale
Guillaume Vogt, The Rockefeller University
Capucine Picard, Paris Descartes University
Lizbeth Blancas Galicia, Paris Descartes University
Carolina Prando, State University of Campinas Medical School
Audrey V. Grant, Paris Descartes University
Christophe C. Marchal, Indiana University School of Medicine
Marjorie Hubeau, Institut National de la Santé et de la Recherche Médicale
Ariane Chapgier, Paris Descartes University
Ludovic de Beaucoudrey, Paris Descartes University
Anne Puel, Paris Descartes University
Jacqueline Feinberg, Paris Descartes University
Ethan Valinetz, Indiana University School of Medicine
Lucile Janniere, Paris Descartes University
Celine Besse, National Genotyping Center
Anne Boland, National Genotyping Center
Jean-Marie Brisseau, Nantes Hospital
Stephane Blanche, Necker Hospital
Olivier Lortholary, Necker Hospital
Claire Fieschi, Saint Louis Hospital
Jean-Francois Emile, Versailles Saint-Quentin-en-Yvelines University
Stephanie Boisson-Dupuis, The Rockefeller University
Saleh Al-Muhsen, King Saud University
Bruce A. Woda, University of Massachusetts Medical SchoolFollow
Peter E. Newburger, University of Massachusetts Medical SchoolFollow
Antonio Condino-Neto, State University of Campinas Medical School
Mary C. Dinauer, University of Massachussetts Medical School
Laurent Abel, The Rockefeller University
Jean-Laurent Casanova, University of Paris René Descartes

UMMS Affiliation

Department of Pediatrics; Department of Pathology

Publication Date


Document Type



Animals; CHO Cells; Cricetinae; Cricetulus; *Genes, X-Linked; *Genetic Predisposition to Disease; Humans; Macrophages; Male; Membrane Glycoproteins; Mutation; NADPH Oxidase; Tuberculosis


Bacterial Infections and Mycoses | Hematology | Oncology | Pediatrics


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.

DOI of Published Version



Nat Immunol. 2011 Mar;12(3):213-21. Epub 2011 Jan 30. Link to article on publisher's website

Journal/Book/Conference Title

Nature immunology

Related Resources

Link to article in PubMed

PubMed ID