Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease
Department of Pediatrics; Department of Pathology
Medical Subject Headings
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.
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Citation: Nat Immunol. 2011 Mar;12(3):213-21. Epub 2011 Jan 30. Link to article on publisher's website