Infection of Endothelial Cells with VirulentRickettsia prowazekiiIncreases the Transmigration of Leukocytes

Abstract

Rickettsia prowazekii, the etiologic agent of epidemic typhus, infects vascular endothelium, leading to vasculitis and tissue infiltration of leukocytes. Murine and human endothelial cells (ECs) were infected with R. prowazekii, including the virulent Breinl strain and the attenuated Madrid E strain. The transendothelial migration (TM) of murine and human peripheral blood mononuclear cells (PBMCs) across ECs infected with Breinl organisms was significantly increased compared with that for uninfected ECs or for ECs infected with attenuated organisms, demonstrating that increased TM was related to R. prowazekii virulence. Increased TM was associated with a specific inflammatory pattern. Indeed, only Breinl organisms induced the expression of transcripts for inflammatory cytokines and chemokines by ECs. Murine PBMCs that had transmigrated across ECs infected with Breinl organisms overexpressed inflammatory cytokines and chemokines as well as tissue factor, whereas interleukin-10 expression was down-regulated. The impact of R. prowazekii infection on the TM of PBMCs may play a prominent role in the development of lesions in epidemic typhus.