Mitogen-activated protein kinases are involved in tumor necrosis factor alpha production in macrophages infected with Orientia tsutsugamushi.

Orientia tsutsugamushi, an obligatory intracellular bacterium, is the causative agent of scrub typhus. Here the role of MAPK in TNF-alpha production in macrophages after infection with O. tsutsugamushi has been investigated. ERK1/2, JNK, and p38 MAPK became phosphorylated in Orientia-stimulated macrophages. Selective inhibitors of MAPK cascades could all significantly reduce Orientia-stimulated TNF-alpha production. Orientia-stimulated TNF-alpha production via p38 and JNK pathways was regulated by a post-transcriptional mechanism, whereas the ERK pathway mainly controlled the transcriptional step of TNF-alpha gene expression during infection. In conclusion, our data indicate that MAPK signaling is required to induce maximal TNF-alpha production in macrophages during Orientia infection.