| Summary: | <p>Abstract</p> <p>Background</p> <p>Human leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis. Human monocytic U937 cells transfected with HLA-B27 are less able to eliminate intracellular <it>Salmonella enterica </it>serovar Enteritidis than those transfected with control HLA antigens (e.g. HLA-A2). To investigate further the mechanisms by which HLA-B27-transfected cells allow increased replication of these bacteria, a DNA-based microarray was used for comparative genomic analysis of <it>S</it>. Enteritidis grown in HLA-B27- or HLA-A2-transfected cells. The microarray consisted of 5080 oligonucleotides from different serovars of <it>Salmonella </it>including <it>S</it>. Enteritidis PT4-specific genes. Bacterial RNA was isolated from the infected HLA-B27- or HLA-A2-transfected cells, reverse-transcribed to cDNA, and hybridized with the oligonucleotides on the microarrays. Some microarray results were confirmed by RT-PCR.</p> <p>Results</p> <p>When gene expression was compared between <it>Salmonella </it>grown in HLA-B27 cells and in HLA-A2 cells, 118 of the 4610 <it>S</it>. Enteritidis-related genes differed in expression at 8 h after infection, but no significant difference was detectable at 2 h after infection. These differentially expressed genes are mainly involved in <it>Salmonella </it>virulence, DNA replication, energy conversion and metabolism, and uptake and metabolism of nutrient substances, etc. The difference suggests HLA-B27-dependent modulation of <it>Salmonella </it>gene expression, resulting in increased <it>Salmonella </it>replication in HLA-B27-positive cells. Among the up-regulated genes were those located in <it>Salmonella </it>pathogenicity island (SPI)-2, which play a central role in intracellular survival and replication of <it>Salmonella</it>.</p> <p>Conclusions</p> <p>This is the first report to show the regulation of <it>Salmonella </it>gene expression by HLA-B27 during infection of host cells. This regulation probably leads to increased <it>Salmonella </it>survival and replication in HLA-B27-positive cells. SPI-2 genes seem to contribute significantly to the increased replication.</p>
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