Induction of Cell Signaling Events by the Cholera Toxin B Subunit in Antigen-Presenting Cells

• Published in: Infection and Immunity Vol. 75; no. 6; pp. 3150 - 3159
• Main Authors: Schnitzler, Aletta C, Burke, Jennifer M, Wetzler, Lee M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.06.2007
• Subjects: Animals; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - physiology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Bacterial diseases; Bacteriology; Biological and medical sciences; Cell Communication; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Cholera; Cholera Toxin - chemistry; Cholera Toxin - pharmacology; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Infectious diseases; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Signal Transduction - drug effects; Signal Transduction - physiology; Tropical bacterial diseases; Infection; Toxin; Microbiology; Vibrio cholerae; Bacteriosis; Bacteria; Vibrionaceae; Accessory cell; Cholera; B-Lymphocyte; Subunit; Immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00581-06

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 without 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 transactivation of the transcription elements cyclic AMP-responsive element and NF-κB, 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 interleukin-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 for elucidating CT-B adjuvant activity in the absence of enzymatically active holotoxin.