Abstract

Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-[alpha]) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium O. tsutsugamushi was investigated. The genes that were upregulated included macrophage inflammatory proteins 1[alpha]/[beta] (MIP-1[alpha]/[beta]), MIP-2, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10 (IP-10), and TNF-[alpha]. Peak expression of these chemokines and TNF-[alpha] was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic increases during infection in the steady-state levels of mRNA coding for the inhibitory subunit of NF-[kappa]B (I[kappa]B[alpha]), whose transcription is enhanced by binding of NF-[kappa]B within the I[kappa]B[alpha] promoter region. Thus, O. tsutsugamushi appears to be a strong inducer of chemokines and TNF-[alpha] which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.

• Keywords: Orientia tsutsugamushi; scrub typhus; peritoneal macrophage; chemokine gene expression; TNF-[alpha]