title: Vibrio cholerae O395 outer membrane vesicles modulate intestinal epithelial cells in a NOD1 protein-dependent manner and induce dendritic cell-mediated Th2/Th17 cell responses.
abstract: Like other Gram-negative pathogens, Vibrio cholerae, the causative agent of the diarrheal disease cholera, secretes outer membrane vesicles (OMVs). OMVs are complex entities composed of a subset of envelope lipid and protein components and play a role in the delivery of effector molecules to host cells. We previously showed that V. cholerae O395 cells secrete OMVs that are internalized by host cells, but their role in pathogenesis has not been well elucidated. In the present study, we evaluated the interaction of OMVs with intestinal epithelial cells. These vesicles induced expression of proinflammatory cytokines such as IL-8 and GM-CSF and chemokines such as CCL2, CCL20, and thymic stromal lymphopoietin in epithelial cells through activation of MAPK and NF-κB pathways in NOD1-dependent manner. Epithelial cells stimulated with OMVs activated dendritic cells (DCs) in a direct co-culture system. Activated DCs expressed high levels of co-stimulatory molecules; released inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-23 and chemokines CCL22 and CCL17; and subsequently primed CD4(+) T cells leading to IL-4, IL-13, and IL-17 expression. These results suggest that V. cholerae O395 OMVs modulate the epithelial proinflammatory response and activate DCs, which promote T cell polarization toward an inflammatory Th2/Th17 response.
authors.affiliation: Molecular and Human Genetics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata 700032, India.
authors.forename: Debashree
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Keya
authors.initials: K
authors.lastname: Chaudhuri
mesh_terms: D002771:Cholera / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020935:MAP Kinase Signaling System / Q000276:immunology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014734:Vibrio cholerae / Q000502:physiology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D020929:Mitogen-Activated Protein Kinase Kinases