Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease
Department of Pediatrics; Department of Pathology
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
Bustamante J, Arias AA, Vogt G, Picard C, Galicia LB, Prando C, Grant AV, Marchal CC, Hubeau M, Chapgier A, de Beaucoudrey L, Puel A, Feinberg J, Valinetz E, Janniere L, Besse C, Boland A, Brisseau J, Blanche S, Lortholary O, Fieschi C, Emile J, Boisson-Dupuis S, Al-Muhsen S, Woda BA, Newburger PE, Condino-Neto A, Dinauer MC, Abel L, Casanova J. (2011). Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease. Hematology/Oncology. https://doi.org/10.1038/ni.1992. Retrieved from https://escholarship.umassmed.edu/peds_hematology/134