Chemokine and cytokine production during Orientia tsutsugamushi infection in mice.

Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus which is histopathologically characterized by inflammatory manifestations, indicating that rickettsiae induce mechanisms that amplify the inflammatory response. To understand the pathogenesis of scrub typhus, we examined chemokine and cytokine production after infection with O. tsutsugamushi in mice. The mRNAs that were upregulated included lymphotactin, RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory proteins 1alpha/beta (MIP-1alpha/beta), MIP-2, monocyte chemoattractant protein 1, lymphotoxin beta, tumor necrosis factor alpha, interleukin-6, gamma-interferon, transforming growth factor beta1, and migration inhibition factor. Peak expression of these chemokines and cytokines was observed between 4 and 8 days after infection. Gene induction was followed by the secretion of chemokine and cytokine proteins. Chemokine profile in infected mice was well correlated with kinetics of inflammatory cell infiltration. Thus, O. tsutsugamushi appears to be a strong inducer of chemokines and cytokines which may, by the attraction and activation of phagocytic leukocytes, significantly contribute to inflammation observed in scrub typhus.