Pasteurella multocida toxin activates human monocyte-derived and murine bone marrow-derived dendritic cells in vitro but suppresses antibody production in vivo.
Pasteurella multocida toxin (PMT) is a potent mitogen for fibroblasts and osteoblastic cells. PMT activates phospholipase C-beta through G(q)alpha, and the activation of this pathway is responsible for its mitogenic activity. Here, we investigated the effects of PMT on human monocyte-derived dendritic cells (MDDC) in vitro and show a novel activity for PMT. In this regard, PMT activates MDDC to mature in a dose-dependent manner through the activation of phospholipase C and subsequent mobilization of calcium. This activation was accompanied by enhanced stimulation of naive alloreactive T cells and dominant inhibition of interleukin-12 production in the presence of saturating concentrations of lipopolysaccharide. Surprisingly, although PMT mimics the activating effects of cholera toxin on human MDDC and mouse bone marrow-derived dendritic cells, we found that PMT is not a mucosal adjuvant and that it suppresses the adjuvant effects of cholera toxin in mice. Together, these results indicate discordant effects for PMT in vitro compared to those in vivo.
Bagley
Kenneth C
KC
Division of Vaccine Research, Institute of Human Virology, University of Maryland Baltimore, 725 W. Lombard St., Baltimore, MD 21201, USA. lewisg@umbi.umd.edu
Abdelwahab
Sayed F
SF
Tuskan
Robert G
RG
Lewis
George K
GK
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016207:Cytokines; C062258:Pasteurella multocida toxin; D018664:Interleukin-12; D000001:Calcimycin; D019284:Thapsigargin; D010047:Ovalbumin; D002772:Cholera Toxin; D010738:Type C Phospholipases; D002118:Calcium