Flagellin-independent regulation of chemokine host defense in Campylobacter jejuni-infected intestinal epithelium.
Campylobacter jejuni is a leading cause of bacterial food-borne diarrheal disease throughout the world and the most frequent antecedent of autoimmune neuropathy Guillain-Barré syndrome. While infection is associated with immune memory, little is known regarding the role of the epithelium in targeting dendritic cells (DC) for initiating the appropriate adaptive immune response to C. jejuni. The objective of this study was to define the role for the intestinal epithelium in the induction of the adaptive immune response in C. jejuni infection by assessing the production of DC and T-cell chemoattractants. Human T84 epithelial cells were used as model intestinal epithelia. Infection of T84 cells with C. jejuni dose- and time-dependently up-regulated DC and T-cell chemokine gene transcription and secretion. Induction required live bacteria and was in the physiologically relevant direction for attraction of mucosal immunocytes. C. jejuni-activated NF-kappaB signaling was shown to be essential for proinflammatory chemokine secretion. Notably, C. jejuni secretion occurred independently of flagellin identification by Toll-like receptor 5. Secretion of a DC chemoattractant by differing clinical C. jejuni isolates suggested adherence/invasion were key virulence determinants of epithelial chemokine secretion. The regulated epithelial expression of DC and T-cell chemoattractants suggests a mechanism for the directed trafficking of immune cells required for the initiation of adaptive immunity in campylobacteriosis. Chemokine secretion occurs despite Campylobacter evasion of the flagellin pattern recognition receptor, suggesting that alternate host defense strategies limit disease pathogenesis.
Johanesen
Priscilla A
PA
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Dwinell
Michael B
MB
D016123:Campylobacter jejuni / Q000276:immunology*; D045744:Cell Line, Tumor; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis; D005408:Flagellin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000502:physiology
C108355:CCL20 protein, human; C114753:CXCL10 protein, human; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D005408:Flagellin