title: Human epithelial cells stimulated with Vibrio cholerae produce thymic stromal lymphopoietin and promote dendritic cell-mediated inflammatory Th2 response.
abstract: Vibrio cholerae induces acute inflammatory response at intestinal epithelial surface; the underlying cellular immune mechanisms for such effects are largely unexplored. Mucosal immune response is controlled by crosstalk between the intestinal epithelial cells (ECs) and dendritic cells (DCs). An EC-derived cytokine thymic stromal lymphopoietin (TSLP) has been found a critical regulator of several human inflammatory conditions. TSLP is highly elevated in ECs stimulated with V. cholerae and its recombinant flagellin (rFlaA). V. cholerae treated human ECs produce DC-attracting chemokine MIP-3α (CCL20). Flagellin, a potent V. cholerae factor was responsible for maximum stimulation of epithelial CCL20 production and subsequent DC activation. Activated DCs express high levels of costimulatory molecules and secrete inflammatory cytokines TNF-α, IL-6 and IL-1β. Bacteria stimulated ECs conditioned DCs to produce Th2 cell-attracting chemokines CCL17 and CCL22. TSLP and other mediators present in the V. cholerae stimulated EC-culture filtrate potently activated DCs, which subsequently primed CD4(+)T cells to differentiate into T helper type 2 (Th2) cells that produce high amounts of IL-4, IL-13 and TNF-α and low IFN-γ. TSLP-induced proinflammatory response in DCs involved the transcriptional mechanisms, MAPKs (ERK1/2, p38 and JNK) and STAT3 activation. This study suggests TSLP and other mediators released from ECs in response to V. cholerae colonization actively influence DCs in initiating inflammatory response.
authors: Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700032, West Bengal, India. bhowmickswati@gmail.com
authors: Swati
authors: S
authors: Bhowmick
authors: Debashree
authors: D
authors: Chatterjee
authors: Keya
authors: K
authors: Chaudhuri
mesh_terms: D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D002771:Cholera / Q000150:complications / Q000276:immunology / Q000382:microbiology; D018920:Coculture Techniques; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation; D014734:Vibrio cholerae / Q000254:growth & development / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D018925:Chemokines; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin