Mycobacterium abscessus alkyl hydroperoxide reductase C promotes cell invasion by binding to tetraspanin CD81.
iScience
; 26(2): 106042, 2023 Feb 17.
Article
en En
| MEDLINE
| ID: mdl-36818301
ABSTRACT
Mycobacterium abscessus (Mab) is an increasingly recognized pulmonary pathogen. How Mab is internalized by macrophages and establishes infection remains unknown. Here, we show that Mab uptake is significantly reduced in macrophages pre-incubated with neutralizing anti-CD81 antibodies or in cells in which the large extracellular loop (LEL) of CD81 has been deleted. Saturation of Mab with either soluble GST-CD81-LEL or CD81-LEL-derived peptides also diminished internalization of the bacilli. The mycobacterial alkyl hydroperoxide reductase C (AhpC) was unveiled as a major interactant of CD81-LEL. Pre-exposure of macrophages with soluble AhpC inhibited mycobacterial uptake whereas overexpression of AhpC in Mab enhanced its internalization. Importantly, pre-incubation of macrophages with anti-CD81-LEL antibodies inhibited phagocytosis of AhpC-coated beads, indicating that AhpC is a direct interactant of CD81-LEL. Conditional depletion of AhpC in Mab correlated with decreased internalization of Mab. These compelling data unravel a previously unexplored role for CD81/AhpC to promote uptake of pathogenic mycobacteria by host cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia