Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells.
Intestinal epithelial cells (IEC) play a central role in innate and acquired mucosal immunity. They ensure early signaling to trigger an inflammatory response against pathogens. Moreover, IEC mediate transcytosis of dimeric IgA (dIgA), through the polymeric-immunoglobulin receptor (pIgR), to provide secretory IgA, the major protective Ig in mucosal secretions. Using an in vitro model of polarized IEC, we describe an additional anti-inflammatory mechanism of dIgA-mediated protection against intracellular bacterial components involved in the proinflammatory activation of IEC. Specific dIgA colocalizes to lipopolysaccharide (LPS) in the apical recycling endosome compartment, preventing LPS-induced NF-kappaB translocation and subsequent proinflammatory response. Thus, intracellular neutralization by dIgA limits the acute local inflammation induced by proinflammatory pathogen-associated molecular patterns such as LPS.
Fernandez
M Isabel
MI
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 28 rue du Dr. Roux, 75015, Paris, France. mifernan@pasteur.fr
Pedron
Thierry
T
Tournebize
Régis
R
Olivo-Marin
Jean Christophe
JC
Sansonetti
Philippe J
PJ
Phalipon
Armelle
A
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation / Q000502:physiology; D007136:Immunoglobulins / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits
D016207:Cytokines; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016328:NF-kappa B