Orientia tsutsugamushi inhibits tumor necrosis factor alpha production by inducing interleukin 10 secretion in murine macrophages

Orientia tsutsugamushi (OT) is the causative agent of scrub typhus or Tsutsugamushi disease. We have previously reported that OT suppresses the production of inflammatory cytokines in murine macrophages. In this study, we examined the mechanism of OT to suppress the tumor necrosis factor alpha (TNF-alpha) production. J774 macrophages were preinfected with OT for various times and then treated with lipopolysaccharide (LPS) for 24 h. Preinfection by OT inhibited LPS-induced production of TNF-alpha, but did not affect the activation of NF-kappaB. This suppression was also induced by the conditioned medium (CM) from OT-infected macrophages. Interestingly, the CM contained a potent interleukin-10 (IL-10)-inducing factor that is active on activated macrophages. Therefore, the IL-10-inducing factor might enhance the negative-feedback mechanism ascribed to IL-10, to allow bacterial survival in the hostile environment of macrophages.