A role for IFNgamma in differential superantigen stimulation of conventional versus plasmacytoid DCs.
Superantigens (SAgs) are known to play a role in food poisoning, toxic shock syndrome and have been identified as a potential mediator of autoimmunity. Although much is known about the effects of SAgs on T cells, by comparison few studies have investigated how SAgs influence innate immune cells. In particular no study has examined how SAgs affect murine plasmacytoid dendritic cells (pDC). We report that in vivo administration of staphylococcal enterotoxin A (SEA) increased the number of pDCs in secondary lymphoid organs, and induced CD86 and CD40 expression. Similar to SEA activation of conventional DCs (cDCs), pDCs relied on T cells, but not on CD40. Nonetheless, pDCs strictly required IFNgamma for upregulation of CD86 and CD40, but cDCs did not depend upon IFNgamma for activation. Further, even though IFNgamma deficient pDCs were not activated by SEA, they were still capable of producing wild-type levels of IFNalpha in response to CpG oligodeoxynucleotide (ODN). The source of IFNgamma for pDC activation was not T cells, nor did pDCs themselves have to synthesize or bind IFNgamma, but the presence of IFNgamma was essential. After SEA stimulation, IFNgamma deficient mice fail to induce expression of the pDC dependent chemokines CXCL9, and demonstrated a defect in recruitment of pDCs to marginal zones of lymphoid organs. Thus, SEA exerts its combined effect on pDC activation, recruitment and chemokine induction through the action of IFNgamma. This fundamental dichotomy of the effects of SAgs on pDCs versus cDCs show how a non-PAMP from bacteria, can selectively and indirectly stimulate innate cell subpopulations much in the same way that differential TLR expression influences cells of the innate immune system.
Muralimohan
Guruprasaadh
G
Department of Immunology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06032, USA.
Vella
Anthony T
AT
D019264:Adoptive Transfer; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
D018089:Superantigens; D007371:Interferon-gamma