A genomic concept in cellular interaction of clinical Campylobacter spp. with human epithelial colorectal adenocarcinoma cells.

Abstract

This study aimed to realize the genomic concept of cellular interaction of clinical Campylobacter spp. with human epithelial colorectal adenocarcinoma cells. It was indicated that the mean adherence and invasion rate of C.jejuni isolates was significantly higher than C.coli and the highest adhesion rate among the C.jejuni and C.coli belonged to strains harboring 4 (flaA, cadF, peb1A, and flpA) and 3 (flaA, cadF, and peb1A) adherence genes, respectively, which indicates that the adhesion potential of C.coli and C.jejuni strains is associated with the coordinate function and cumulative effect of selected virulence-associated genes. The highest invasion rate in C.jejuni (10.3%) and C.coli (8.4%) isolates belonged to strains which concomitantly contained 3 (ciaB, iamA, and tlp1) and 2 (ciaB and iamA) invasion-associated genes which emphasizes on the cooperative roles of these genes in C.jejuni and C.coli invasion to Caco-2 cells. The toxicity of C.jejuni for Caco-2 cells was proved higher than that of C.coli. There was a positive correlation between adherence, invasion and toxicity of both C.jejuni and C.coli isolates. Moreover, the expression levels of CDT-producing genes in C.jejuni strains was significantly higher than that of C.coli. The average cytotoxicity of the strains with all three CDT-encoding genes (cdtA, cdtB and cdtC) was statistically higher than those lacking one or more CDT subunits. A crucial contribution of CdtB to the cytotoxicity of Campylobacter strains was detected. Following the treatment of epithelial cells with C.jejuni or C.coli, IL-8 and TNF-α were significantly increased compared to untreated Caco-2 cells, and the highest IL-8 expression was observed in both C.jejuni and C.coli expressing all CDTs (cdtA, cdtB, and cdtC). We, for the first time, indicated the major contribution of TLR2 and TLR4 in campylobacter initiation of pathogenesis, while increased invasiveness and cytotoxicity was significantly associated with the increased expression of TLR4 in C.jejuni isolates.