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[subscript q][alpha], and the activation of this pathway is responsible for its mitogenic activity. Here, we investigated the effects of PMT on human monocyte-d...

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Bibliographic Details
Published in:Infection and Immunity 2005, Vol.73 (1), p.413-421
Main Authors: Bagley, Kenneth C, Abdelwahab, Sayed F, Tuskan, Robert G, Lewis, George K
Format: Article
Language:English
Subjects:
Animals
Antibody Formation - drug effects
Bacterial Proteins - pharmacology
Bacterial Toxins - pharmacology
Bacteriology
Biological and medical sciences
Bone Marrow Cells - cytology
Calcimycin - pharmacology
Calcium - metabolism
Cholera Toxin - antagonists & inhibitors
Cytokines - biosynthesis
Dendritic Cells - drug effects
Dendritic Cells - physiology
Dose-Response Relationship, Drug
Female
Fundamental and applied biological sciences. Psychology
Host Response and Inflammation
Humans
Immune Tolerance - drug effects
Interleukin-12 - biosynthesis
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Microbiology
Miscellaneous
Monocytes - cytology
Ovalbumin - immunology
Pasteurella multocida
T-Lymphocytes - immunology
Thapsigargin - pharmacology
Type C Phospholipases - physiology
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Summary:Pasteurella multocida toxin (PMT) is a potent mitogen for fibroblasts and osteoblastic cells. PMT activates phospholipase C-[beta] through G[subscript 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 nai̊ve 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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.73.1.413-421.2005