Orientia tsutsugamushi suppresses the production of inflammatory cytokinesinduced by its own heat-stable component in murine macrophages

Orientia tsutsugamushi is a Gram-negative obligate intracellular bacterium, which causes scrub typhus. To understand the pathogenesis of scrub typhus, we have investigated the induction of tumor necrosis alpha (TNF-alpha) and interleukin-6 (IL-6) by O. tsutsugamushi in two murine macrophage cell lin es. Both live and heat-killed orientia stimulated the production of cytokin es in J774A.1 cells. Polymyxin B does not affect the secretion of cytokines . These together with the fact that the immature macrophage cell line, P388 D1, did not produce,TNF-alpha when induced by either live or heat-killed O. tsutsugamushi strongly argue against any roles of lipopolysaccharide (LPS) in cytokine production. Furthermore, the result that the cytokine response s were more brisk when macrophage cell lines had been induced by heat-kille d O. tsutsugamushi than by live organisms strongly suggest that a heat-stab le molecule might be responsible for the induction of cytokine production a nd O. tsutsugamushi might have mechanisms suppressing the production of inf lammatory cytokines induced by its own heat-stable molecule. (C) 2001 Acade mic Press.