We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Engagement of CD46 andα5β1 integrin by group A streptococci is required for efficient invasion of epithelial cells.
- Authors
Rezcallah, Myrna S.; Hodges, Kimberly; Gill, Darcy B.; Atkinson, John P.; Wang, Beinan; Cleary, P. Patrick
- Abstract
Membrane cofactor protein (MCP or CD46), a widely distributed complement regulatory human protein, is a cell surface receptor for many pathogens including group A streptococci (GAS). The surface M protein of GAS binds CD46 and mediates GAS adherence to keratinocytes. In the present study, we studied the role of CD46 in GAS invasion of human lung epithelial cells, A549. Anti-CD46 antibody which specifically blocks the domain to which M protein binds inhibited adherence to and invasion of A549 cells by GAS. Moreover, downregulation of CD46 expression on A549 by RNA interference resulted in reduced invasion of these cells by GAS. A mutant form of CD46 with a deletion in the cytoplasmic domain was overexpressed in A549 cells, which resulted in partial inhibition of invasion. This indicates that the cytoplasmic tail is required for CD46 to promote invasion by GAS. Invasion assays withLactococcus lactisthat express M protein demonstrated the dependence of CD46-promoted invasion on interaction with M protein. In addition, CD46-mediated invasion was also found to be dependent on the extracellular matrix protein fibronectin.
- Subjects
PROTEIN S; EXTRACELLULAR matrix proteins; CELL membranes; PATHOGENIC microorganisms; KERATINOCYTES; EPITHELIAL cells
- Publication
Cellular Microbiology, 2005, Vol 7, Issue 5, p645
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/j.1462-5822.2004.00497.x