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Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte‐derived dendritic cells and dominantly inhibit cytokine production through a cAMP‐dependent pathway
Author(s) -
Bagley Kenneth C.,
Abdelwahab Sayed F.,
Tuskan Robert G.,
Fouts Timothy R.,
Lewis George K.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.5.962
Subject(s) - forskolin , adenylate cyclase toxin , pertussis toxin , biology , bordetella pertussis , cyclase , adenylate kinase , adenosine , cholera toxin , microbiology and biotechnology , cytokine , monocyte , cyclic adenosine monophosphate , signal transduction , g protein , receptor , biochemistry , immunology , bacteria , genetics
Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis . PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte‐derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5′‐diphosphate‐ribosylation‐defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl‐cAMP (d‐cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP‐dependent kinase inhibitors blocked the ability of PT, AT, d‐cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on MDDC are mediated strictly by cAMP.

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