Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease.
Nat Immunol
; 12(3): 213-21, 2011 Mar.
Article
in En
| MEDLINE
| ID: mdl-21278736
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.
Full text:
1
Database:
MEDLINE
Main subject:
Tuberculosis
/
Membrane Glycoproteins
/
NADPH Oxidases
/
Genetic Predisposition to Disease
/
Genes, X-Linked
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Macrophages
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2011
Type:
Article
Affiliation country:
France