Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells.
Live cells of Campylobacter jejuni and Campylobacter coli can induce release of interleukin-8 (IL-8) from INT407 cells. Additionally, membrane fractions of C. jejuni 81-176, but not membrane fractions of C. coli strains, can also induce release of IL-8. Membrane preparations from 81-176 mutants defective in any of the three membrane-associated protein subunits of cytolethal distending toxin (CDT) were unable to induce IL-8. The presence of the three cdt genes on a shuttle plasmid in trans restored both CDT activity and the ability to release IL-8 to membrane fractions. However, CDT mutations did not affect the ability of 81-176 to induce IL-8 during adherence to or invasion of INT407 cells. When C. jejuni cdt genes were transferred on a shuttle plasmid into a C. coli strain lacking CDT, membrane preparations became positive in both CDT and IL-8 assays. Growth of C. jejuni in physiological levels of sodium deoxycholate released all three CDT proteins, as well as CDT activity and IL-8 activity, from membranes into supernatants. Antibodies against recombinant forms of each of the three CDT subunit proteins neutralized both CDT activity and the activity responsible for IL-8 release. The data suggest that C. jejuni can induce IL-8 release from INT407 cells by two independent mechanisms, one of which requires adherence and/or invasion and the second of which requires CDT.
Hickey
T E
TE
Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
McVeigh
A L
AL
Scott
D A
DA
Michielutti
R E
RE
Bixby
A
A
Carroll
S A
SA
Bourgeois
A L
AL
Guerry
P
P
D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D002478:Cells, Cultured; D004926:Escherichia coli / Q000472:pathogenicity; D005816:Genetic Complementation Test; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001427:Bacterial Toxins; D016209:Interleukin-8; C067044:cytolethal distending toxin