Cleavage of p65 Subunit of NF-kappaB by Orientia tsutsugamushi

ABSTRACT

Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular parasite and usually propagates in the cytoplasm of host endothelial cells and macrophages. Macrophages are the first defense line against bacterial infection and NF-kappaB is activated upon contact with bacteria, resulting in the transcription of inflammatory cytokine to control bacterial infection. In this study, we investigated whether O. tsutsugamushi modulates NF-kappaB activation in the macrophages. We examined the changes of NF-kappaB proteins upon infection with O. tsutsugamushi and found that NF-kappaB is activated at a slow rate as judged with EMSA and immunoblot analysis. Interestingly, we found that p65 was cleaved generating a 45 kDa fragment. In addition, fragment of p65 is generated only by the virulent serotype strain of O. tsutsugamushi, suggesting this cleavage may be associated with the mouse virulence. It is still unknown whether this is a direct result of O. tsutsugamushi proteins or enzymes of host cell. Further exploration of the mechanism that modulates NF-kappaB activity by O. tsutsugamushi could contribute to a better understanding of the molecular pathogenesis of O. tsutsugamushi infection.