HLA-B27 modulates intracellular growth of Salmonella pathogenicity island 2 mutants and production of cytokines in infected monocytic U937 cells

• Published in: PloS one 2012-03, Vol.7 (3), p.e34093-e34093
• Main Authors: Ge, Shichao, He, Qiushui, Granfors, Kaisa
• Format: Article
• Language: English
• Subjects: Antigens; Arthritis; Bacteria; Bacterial infections; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms; Biology; Cell survival; Cellulose; Cytokines; Cytokines - metabolism; Deoxyribonucleic acid; Disruption; DNA; DNA Replication; E coli; Escherichia coli; Gene disruption; Gene expression; Genes; Genetic aspects; Growth rate; Health aspects; Histocompatibility antigen HLA; HLA-A2 Antigen - genetics; HLA-A2 Antigen - metabolism; HLA-B27 Antigen - genetics; HLA-B27 Antigen - metabolism; Humans; Infection; Infections; Infectious diseases; Interleukin 10; Interleukin-10 - metabolism; Interleukins; Intracellular; Lymphatic system; Lymphoma; Medical research; Medicine; Membrane Proteins - genetics; Membrane Proteins - metabolism; Monocytes; Monocytes - metabolism; Monocytes - microbiology; Mutants; Mutation; Pathogenesis; Pathogenicity; Pathogens; Replication; Rodents; Salmonella; Salmonella Enteritidis; Salmonella enteritidis - genetics; Salmonella enteritidis - growth & development; Signal transduction; Transfection; Tuberculosis; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; U937 Cells; Up-Regulation; Virulence; Virulence (Microbiology); Virulence factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034093

Salmonella enterica serovar Enteritidis PT4 KS8822/88 replicates rapidly in HLA-B27-transfected human monocytic U937 cells. In this process, Salmonella pathogenicity island 2 (SPI-2) genes play a crucial role. Our previous study indicated that 118 Salmonella genes, including 8 SPI-2 genes were affected by HLA-B27 antigen during Salmonella infection of U937 cells. To further investigate Salmonella replication in HLA-B27-positive U937 monocytic cells, two SPI-2 genes, ssaS and sscA up-regulated most during Salmonella infection of HLA-B27-transfected U937 cells, were mutated by using one-step gene disruption method. Intracellular survival and replication of the mutants in the U937 cells was compared to that of the wild type strain. Surprisingly, the two mutated strains replicated significantly more than the wild type bacteria in HLA-B27-transfected cells. Secretion of tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) was significantly induced during the infection of HLA-B27-transfected U937 cells with the mutants. The results indicated that the certain SPI-2 genes in wild type bacteria suppress Salmonella intracellular growth and production of cytokines in infected HLA-B27-transfected cells. HLA-B27-associated modulation of Salmonella SPI-2 genes and cytokine production may have importance in the persistent infection of the bacteria and the pathogenesis of reactive arthritis. The study provides evidence that certain virulence factors of pathogens can reduce the intracellular growth in the host cells. We suggest that the limiting intracellular growth might be a strategy for persistence of bacteria in host cells, keeping a balance between pathogenic growth and pathogenesis.