In:
The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 228, No. 6 ( 2023-09-15), p. 777-782
Abstract:
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA−/−) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/−) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA−/−, GBA+/− and GBA+/+ hiPSCs showed that GBA mutation correction restores normal macrophage functions: GCase activity, motility, and phagocytosis. Furthermore, infection of GBA−/−, GBA+/− and GBA+/+ macrophages with the Mycobacterium tuberculosis H37Rv strain showed that impaired mobility and phagocytic activity were correlated with reduced levels of bacterial engulfment and replication suggesting that GD may be protective against tuberculosis.
Type of Medium:
Online Resource
ISSN:
0022-1899
,
1537-6613
DOI:
10.1093/infdis/jiad141
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
1473843-0
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