Suppression of experimental autoimmune encephalomyelitis by extracellular adherence protein of Staphylococcus aureus.
Multiple sclerosis (MS) is a devastating inflammatory disorder of the central nervous system (CNS). A major hallmark of MS is the infiltration of T cells reactive against myelin components. T cell infiltration is mediated by the interaction of integrins of the beta1 and beta2 family expressed by lymphocytes with their endothelial counter-receptors, vascular cell adhesion molecule 1 and intercellular adhesion molecule (ICAM)-1, respectively. We have reported previously that extracellular adherence protein (Eap) of Staphylococcus aureus exerts antiinflammatory activities by interacting with ICAM-1 and blocking beta2-integrin-dependent neutrophil recruitment. Here, we report that Eap inhibits experimental autoimmune encephalomyelitis (EAE) in mice. In vitro, Eap reduced adhesion of peripheral blood T cells to immobilized ICAM-1 as well as their adhesion and transmigration of TNF-activated human endothelium under static and shear flow conditions. These inhibitory effects were corroborated in two mouse models of inflammation. In a delayed-type hypersensitivity model, both T cell infiltration and the corresponding tissue edema were significantly reduced by Eap. In addition, Eap administration prevented the development of EAE and markedly decreased infiltration of inflammatory cells into the CNS. Strikingly, intervention with Eap after the onset of EAE suppressed the disease. Collectively, our findings indicate that Eap represents an attractive treatment for autoimmune neuroinflammatory disorders such as MS.
Xie
Changping
C
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Alcaide
Pilar
P
Geisbrecht
Brian V
BV
Schneider
Darius
D
Herrmann
Mathias
M
Preissner
Klaus T
KT
Luscinskas
Francis W
FW
Chavakis
Triantafyllos
T
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000627:therapeutic use*; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology / Q000473:pathology
D001426:Bacterial Proteins; C444739:Eap-N protein, Staphylococcus aureus; D016601:RNA-Binding Proteins; D018799:Intercellular Adhesion Molecule-1