title: The Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production.
abstract: 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-alpha by 330-, 290- and 550-fold respectively. Moreover, VCC-induced cytokine production is dependent on increased cytosolic Ca(2+) and on the presence of the Src family kinases Lyn and Fyn, known to be required for FcepsilonRI-dependent activation of mast cells. These findings strongly suggest that VCC has a pro-inflammatory activity promoting a Th2-type immune profile.
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via G. Colombo 3, 35121 Padua, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Arcidiacono
authors.forename: Sandra
authors.initials: S
authors.lastname: Odom
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Paccani
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
authors.forename: Carlo
authors.initials: C
authors.lastname: Pucillo
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D015847:Interleukin-4; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium