Orientia tsutsugamushi suppresses the production of inflammatory cytokines induced 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 lines. Both live and heat-killed orientia stimulated the production of cytokines in J774A.1 cells. Polymyxin B does not affect the secretion of cytokines. These together with the fact that the immature macrophage cell line, P388D1, 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 responses were more brisk when macrophage cell lines had been induced by heat-killed O. tsutsugamushi than by live organisms strongly suggest that a heat-stable molecule might be responsible for the induction of cytokine production and O. tsutsugamushi might have mechanisms suppressing the production of inflammatory cytokines induced by its own heat-stable molecule.