Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production

• Published in: Cellular microbiology Vol. 10; no. 4; pp. 899 - 907
• Main Authors: Arcidiacono, Diletta, Odom, Sandra, Frossi, Barbara, Rivera, Juan, Paccani, Silvia R, Baldari, Cosima T, Pucillo, Carlo, Montecucco, Cesare, de Bernard, Marina
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-04-2008; Blackwell Publishing Ltd; Hindawi Limited
• Subjects: Animals; Calcium - metabolism; Cell Line; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Humans; Interleukin-4 - genetics; Interleukin-4 - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Mice, Knockout; Perforin - genetics; Perforin - metabolism; Perforin - pharmacology; Proto-Oncogene Proteins c-fyn - genetics; Proto-Oncogene Proteins c-fyn - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; src-Family Kinases - genetics; src-Family Kinases - metabolism; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Vibrio cholerae - metabolism
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2007.01092.x

Many strains of Vibrio cholerae produce a cytolysin (VCC) that forms oligomeric transmembrane pores responsible for vacuolization of several cell types in culture. Here we suggest that VCC could contribute to the T helper 2 (Th2) response seen in the natural infection; acting through TLR2, VCC enhances mast cells secretion of IL-4, IL-6 and TNF-α by 330-, 290- and 550-fold respectively. Moreover, VCC-induced cytokine production is dependent on increased cytosolic Ca²⁺ and on the presence of the Src family kinases Lyn and Fyn, known to be required for FcεRI-dependent activation of mast cells. These findings strongly suggest that VCC has a pro-inflammatory activity promoting a Th2-type immune profile.