Differential Host Chemkine Response to Helicobacter pylori

Abstract

Purpose: Helicobacter pylori infection is one of the most common infections worldwide. Although most of the cases are asymptomatic, some induce a vigorous immune response. Hp is a genetically diverse bacteria, and infection generally occurs with multiple strains. Hence, we hypothesized that some Hp strains may suppress robust host response induced by virulent strains. The gastric epithelium secretes chemokines in response to Hp infection. Strains that encode cag pathogenicity island activate transcription factor NF-κB, resulting in induction of IL-8 gene expression. The objectives of this study was to determine whether strain SS1, a weak inducer of host chemokine response had a suppressive effect on more virulent clinical strains. Methods: 489 patients in Chennai, South India were screened by endoscopy. Multiple gastric biopsies were obtained for rapid urease test, histopathology and culturing Hp. CagA and VacA (s1/s2, m1/m2) status were determined by RT-PCR. For Hp-mediated host chemokine response, IL-8 mRNA expression was determined in AGS cells, a human gastric epithelial cell line by Real Time RT-PCR. For NF-κB activation, EMSA assays were performed with nuclear extracts. Results: Rapid urease test was positive in 205 patients, of which 110 had positive cultures for Hp. While 89% of the isolates were resistant to metronidazole, only 11% were resistant to both metronidazole and clarithromycin, and <1% had quadruple resistance to metronidazole, amoxycillin, clarithromycin and ciprofloxacin. We next determined the status of Cag A and VacA by PCR. 35/43 of strains encoded CagA, 35/43 strains were vacAs1, and 38/43 were m1. To determine host IL-8 response, we chose two of these strains (CH1 and CH8), both being CagA+, VacAs1m1. AGS cells were either infected with strains CH1, CH8, and SS1 (CagA+, VacAs2m2), individually or together. Both, CH1 and CH8 robustly induced, while SS1 only modestly induced IL-8 mRNA expression. Furthermore, SS1 significantly suppressed the CH1- or CH8-mediated induction of IL-8 expression. Moreover, SS1 inhibited the CH1- and CH-8-mediated activation of NF-κB. Conclusions: The ability of strain SS1 to suppress the vigorous IL-8 induction mediated by the other strains suggests that a critical balance in strain-specific infection may determine the degree of chemokine response from the grastric epithelium.