Enhancement of Th2 pathways and direct activation of B cells by the gingipains of Porphyromonas gingivalis.
Porphyromonas gingivalis cysteine proteinases (gingipains) have been associated with virulence in destructive periodontitis, a disease process that has been linked with Th2 pathways. Critical in maintaining Th2 activity is the response of B lymphocytes to environmental interleukin (IL)-4, a cytokine that also counteracts Th1-cell differentiation. Here we demonstrate that while the gingipains effectively degrade interleukin (IL)-4 under serum-free conditions, limited hydrolysis was observed in the presence of serum even after prolonged incubation. Gingipains up-regulated CD69 expression directly in purified peripheral blood B cell preparations. Further, the induction of IL-4 receptor expression on B cells by gingipains correlates with B cell activation, which is also manifested by a mitogenic response. These results suggest that the gingipains of P. gingivalis act during the early stage of B-cell growth as a competence signal, whereby sensitized B cells might become more responsive to further challenge in the disease-susceptible individual.
Yun
L W P
LW
Institute of Dental Research, Centre for Oral Health, Wentworthville, Sydney, New South Wales, Australia. plwyun@yahoo.com
Decarlo
A A
AA
Collyer
C
C
Hunter
N
N
D018829:Adhesins, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology*; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D015847:Interleukin-4 / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D000099192:CD69 Antigens
D018829:Adhesins, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003546:Cysteine Endopeptidases; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D015847:Interleukin-4; D037181:Lectins, C-Type; D019948:Receptors, Interleukin-4; D000099192:CD69 Antigens