PMID- 20670450 OWN - NLM STAT- MEDLINE DCOM- 20100916 LR - 20211203 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 11 DP - 2010 Jul 30 TI - Microarray analysis of response of Salmonella during infection of HLA-B27- transfected human macrophage-like U937 cells. PG - 456 LID - 10.1186/1471-2164-11-456 [doi] AB - BACKGROUND: 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 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. RESULTS: When 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. CONCLUSIONS: This 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. FAU - Ge, Shichao AU - Ge S AD - Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Turku, Finland. FAU - Danino, Vittoria AU - Danino V FAU - He, Qiushui AU - He Q FAU - Hinton, Jay C D AU - Hinton JC FAU - Granfors, Kaisa AU - Granfors K LA - eng GR - Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100730 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (DNA, Bacterial) RN - 0 (HLA-B27 Antigen) RN - 0 (PHB2 protein, human) RN - 0 (Prohibitins) RN - 0 (Reactive Oxygen Species) SB - IM MH - DNA Replication MH - DNA, Bacterial/genetics/metabolism MH - Gene Expression Regulation, Bacterial MH - HLA-B27 Antigen/*immunology MH - Humans MH - Oligonucleotide Array Sequence Analysis MH - Prohibitins MH - Reactive Oxygen Species/metabolism MH - Salmonella/*genetics/physiology MH - U937 Cells PMC - PMC3091652 EDAT- 2010/07/31 06:00 MHDA- 2010/09/18 06:00 PMCR- 2010/07/30 CRDT- 2010/07/31 06:00 PHST- 2009/12/03 00:00 [received] PHST- 2010/07/30 00:00 [accepted] PHST- 2010/07/31 06:00 [entrez] PHST- 2010/07/31 06:00 [pubmed] PHST- 2010/09/18 06:00 [medline] PHST- 2010/07/30 00:00 [pmc-release] AID - 1471-2164-11-456 [pii] AID - 10.1186/1471-2164-11-456 [doi] PST - epublish SO - BMC Genomics. 2010 Jul 30;11:456. doi: 10.1186/1471-2164-11-456.