Microbial immune suppression mediated by direct engagement of inhibitory Fc receptor.
A microbial polysaccharide (glucuronoxylomannan (GXM)) exerts potent immunosuppression by direct engagement to immunoinhibitory receptor FcgammaRIIB. Activation of FcgammaRIIB by GXM leads to the recruitment and phosphorylation of SHIP that prevents IkappaBalpha activation. The FcgammaRIIB blockade inhibits GXM-induced IL-10 production and induces TNF-alpha secretion. GXM quenches LPS-induced TNF-alpha release via FcgammaRIIB. The addition of mAb to GXM reverses GXM-induced immunosuppression by shifting recognition from FcgammaRIIB to FcgammaRIIA. These findings indicate a novel mechanism by which microbial products can impair immune function through direct stimulation of an inhibitory receptor. Furthermore, our observations provide a new mechanism for the ability of specific Ab to reverse the immune inhibitory effects of certain microbial products.
Monari
Claudia
C
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Kozel
Thomas R
TR
Paganelli
Francesca
F
Pericolini
Eva
E
Perito
Stefano
S
Bistoni
Francesco
F
Casadevall
Arturo
A
Vecchiarelli
Anna
A
D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D003455:Cryptococcus neoformans / Q000276:immunology; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D000072181:Inositol Polyphosphate 5-Phosphatases; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011134:Polysaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; C000606204:NFKBIA protein, human; D011134:Polysaccharides; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; C027478:glucuronoxylomannan; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases