The Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production.
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.
Arcidiacono
Diletta
D
Department of Biomedical Sciences, University of Padua, Via G. Colombo 3, 35121 Padua, Italy.
Odom
Sandra
S
Frossi
Barbara
B
Rivera
Juan
J
Paccani
Silvia R
SR
Baldari
Cosima T
CT
Pucillo
Carlo
C
Montecucco
Cesare
C
de Bernard
Marina
M
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
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