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Int J Biochem Cell Biol. 2012 Nov;44(11):1779-90. doi: 10.1016/j.biocel.2012.06.030. Epub 2012 Jun 27.

Human epithelial cells stimulated with Vibrio cholerae produce thymic stromal lymphopoietin and promote dendritic cell-mediated inflammatory Th2 response.

Author information

1
Molecular and Human Genetics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700032, West Bengal, India. bhowmickswati@gmail.com

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.

PMID:
22750414
DOI:
10.1016/j.biocel.2012.06.030
[Indexed for MEDLINE]

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