Differential Immune Phenotypes in Human Monocytes Induced by Non-Host-Adapted Salmonella enterica Serovar Choleraesuis and Host-Adapted S . Typhimurium.

We studied the effects of two Salmonella enterica serovar Typhimurium (host-adapted) strains (14028 and 4/74) and three S Choleraesuis (non-host-adapted) strains (A50, A45, and B195) in human monocytes between 2 and 24 h postinfection (p.i.) to investigate whether differences in immune response may explain the much higher prevalence of sepsis in individuals infected with S Choleraesuis. Both serovars significantly increased the production of cytokines associated with acute sepsis (tumor necrosis factor alpha [TNF-α], interleukin β [IL-β], and IL-6), but temporal differences occurred between these serovars and between different S Choleraesuis strains. Generally, all S Choleraesuis strains induced significantly higher production of inflammatory cytokines than S Typhimurium strains (P < 0.01 to 0.05). All S Choleraesuis strains very significantly increased IL-10 production by monocytes at 6 and 24 h p.i. in comparison to S Typhimurium strains ( P < 0.01). In addition, ∼80% of monocytes were viable at 24 h p.i. with S Choleraesuis A50, compared to only ∼40% following S Typhimurium infection. Using S Typhimurium 14028 and S Choleraesuis A50 as examples of these two serovars, we also showed differential expression of genes within the Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) (JAK/STAT) pathway via quantitative PCR (qPCR) microarray analysis. High serum IL-10 concentration and monocyte survival have been reported as markers of the development of human sepsis. We therefore conclude that high production of IL-10 by monocytes may, in part, explain the greater propensity for S Choleraesuis to induce human sepsis and that this may be greater in strains such as A50, which induces both high IL-10 production and monocyte survival.