Abstract
BackgroundHuman 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 Salmonella enterica 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 S. Enteritidis grown in HLA-B27- or HLA-A2-transfected cells. The microarray consisted of 5080 oligonucleotides from different serovars of Salmonella including S. 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.ResultsWhen gene expression was compared between Salmonella grown in HLA-B27 cells and in HLA-A2 cells, 118 of the 4610 S. 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 Salmonella virulence, DNA replication, energy conversion and metabolism, and uptake and metabolism of nutrient substances, etc. The difference suggests HLA-B27-dependent modulation of Salmonella gene expression, resulting in increased Salmonella replication in HLA-B27-positive cells. Among the up-regulated genes were those located in Salmonella pathogenicity island (SPI)-2, which play a central role in intracellular survival and replication of Salmonella.ConclusionsThis is the first report to show the regulation of Salmonella gene expression by HLA-B27 during infection of host cells. This regulation probably leads to increased Salmonella survival and replication in HLA-B27-positive cells. SPI-2 genes seem to contribute significantly to the increased replication.
Highlights
Human leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis
HLA-A2 transfected cells were used as a negative control since it is a common tissue antigen that is not related to the development of ReA [34]
More bacteria were recovered from HLA-B27-expressing cells than HLA-A2-expressing cells at 8 h and even up to 24 h post infection, suggesting that HLA-B27-transfected cells become permissive for intracellular Salmonella survival and replication, which is consistent with our previous studies [32,33,34]
Summary
Human leukocyte antigen (HLA)-B27 is strongly associated with the development of reactive arthritis (ReA) in humans after salmonellosis. The acute gastrointestinal infection caused by Salmonella may result in complications such as reactive arthritis (ReA) [4,5,6]. ReA is an asymmetric polyarthritis and the Macrophages are important in the pathogenesis of Salmonella infections. They are an integral part of the immune response as they present antigens to the innate defence system and communicate with the adaptive immune system to resist the bacterial infection [10,11,12]. Salmonella encounter intracellular host defence mechanisms, including reactive oxygen and nitrogen species (ROS and RNS), antimicrobial peptides, lysosomal enzymes, and adaptive immune responses [10,12]. In order to survive in the host and to avoid clearance by the host immune system, Salmonella express virulence factors to deal with this stressful environment [14]
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