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Infect. Immun. doi:10.1128/IAI.00581-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Induction of cell signaling events by cholera toxin B-subunit in antigen presenting cells

Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Medicine, Boston University School of Medicine, Boston MA 02118, USA

^* To whom correspondence should be addressed. Email: lwetzler{at}bu.edu.

	Abstract

Cholera toxin (CT) is one of the most effective and widely studied mucosal adjuvants. Although the ADP-ribosylating A-subunit has been implicated in augmenting immune responses, the receptor binding B-subunit (CT-B) has greater immunogenicity, and may be a repository of adjuvant activity, absent of potential toxicity. In order to elucidate mechanisms of immune modulation by CT-B alone, primary B cells and macrophages were assessed for responses to CT-B, in vitro, as measured by the expression of cell surface markers, cellular signaling events and cytokine secretion. Increased phosphorylation of multiple signaling molecules including Erk1/2 and p38 was detected. CT-B also induced the transactivation of the transcription elements CRE and NF-B, the latter of which was inhibited by phosphotyrosine inhibition. While specific inhibition of MEK1/2 did not reduce CT-B induction of cell surface marker expression, it did attenuate CT-B mediated IL-6 secretion. These data show that CT-B induces a set of signaling events related to cellular activation, surface molecule expression and cytokine production that has potential implications in elucidating CT-B adjuvant activity in the absence of enzymatically active holotoxin.