Transient Suppression of Shigella flexneri Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA

Autor: Nicholas J. Mantis, Tia Bumpus, Stephen J. Forbes, Elizabeth A. McCarthy, Blaise Corthésy
Rok vydání: 2011
Předmět:
Immunoglobulin A
Cytoplasm
Time Factors
Virulence Factors
Observation
Microbiology
Membrane Potentials
Shigella flexneri
Type three secretion system
Mice
03 medical and health sciences
Adenosine Triphosphate
Immune system
Bacterial Proteins
Antigen
Virology
Animals
Secretion
030304 developmental biology
0303 health sciences
Adenosine Triphosphate/analysis
Antibodies
Bacterial/immunology
Antibodies
Bacterial/isolation & purification
Antibodies
Monoclonal/immunology
Antibodies
Monoclonal/isolation & purification
Bacterial Proteins/secretion
Cell Membrane/physiology
Cytoplasm/chemistry
Immunoglobulin A/immunology
Immunoglobulin A/isolation & purification
Membrane Transport Proteins/metabolism
O Antigens/immunology
Shigella flexneri/immunology
Shigella flexneri/metabolism
Virulence Factors/metabolism
biology
030306 microbiology
Cell Membrane
Antibodies
Monoclonal
Membrane Transport Proteins
O Antigens
biology.organism_classification
Antibodies
Bacterial
Intestinal epithelium
QR1-502
3. Good health
biology.protein
Antibody
Zdroj: mBio
mBio, Vol 2, Iss 3 (2011)
mBio, vol. 2, no. 3, pp. e00042-e00011
ISSN: 2150-7511
2161-2129
DOI: 10.1128/mbio.00042-11
Popis: Mucosal immunity to the enteric pathogen Shigella flexneri is mediated by secretory IgA (S-IgA) antibodies directed against the O-antigen (O-Ag) side chain of lipopolysaccharide. While secretory antibodies against the O-Ag are known to prevent bacterial invasion of the intestinal epithelium, the mechanisms by which this occurs are not fully understood. In this study, we report that the binding of a murine monoclonal IgA (IgAC5) to the O-Ag of S. flexneri serotype 5a suppresses activity of the type 3 secretion (T3S) system, which is necessary for S. flexneri to gain entry into intestinal epithelial cells. IgAC5’s effects on the T3S were rapid (5 to 15 min) and were coincident with a partial reduction in the bacterial membrane potential and a decrease in intracellular ATP levels. Activity of the T3S system returned to normal levels 45 to 90 min following antibody treatment, demonstrating that IgAC5’s effects were transient. Nonetheless, these data suggest a model in which the association of IgA with the O-Ag of S. flexneri partially de-energizes the T3S system and temporarily renders the bacterium incapable of invading intestinal epithelial cells.
IMPORTANCE Secretory IgA (S-IgA) serves as the first line of defense against enteric infections. However, despite its well-recognized role in mucosal immunity, relatively little is known at the molecular level about how this class of antibody functions to prevent pathogenic bacteria from penetrating the epithelial barrier. It is generally assumed that S-IgA functions primarily by “immune exclusion,” a phenomenon in which the antibody binds to microbial surface antigens and thereby promotes bacterial agglutination, entrapment in mucus, and physical clearance from the gastrointestinal tract via peristalsis. The results of the present study suggest that in addition to serving as a physical barrier, S-IgA may have a direct impact on the ability of microbial pathogens to secrete virulence factors required for invasion of intestinal epithelial cells.
Databáze: OpenAIRE
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