Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages

Microb Pathog. 2013 Feb;55:55-63. doi: 10.1016/j.micpath.2012.10.001. Epub 2012 Oct 23.

Abstract

Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, a bacterium that primarily infects endothelial cells both in vitro and in vivo. Evidence suggests that the interaction of O. tsutsugamushi with myeloid cells may play a pivotal role in O. tsutsugamushi infection. We demonstrated that O. tsutsugamushi replicated within human monocyte-derived macrophages. Bacteria stimulated the expression of a large number of genes, including type I interferon genes, interferon-stimulated genes, inflammation-associated genes and apoptosis-related genes, and the release of inflammatory cytokines such as Tumor Necrosis Factor and interleukin-1β. In addition, O. tsutsugamushi induced an M1-type genetic program in macrophages. O. tsutsugamushi viability was required for the type I interferon response and, to a lesser degree, for the inflammatory response. As interferon-γ is known to elicit M1 polarization, we assessed the effect of interferon-γ on the fate of O. tsutsugamushi in macrophages. Exogenous interferon-γ partially inhibited O. tsutsugamushi replication within macrophages. Our results suggest that the inflammatory response induced by O. tsutsugamushi may account for the local and systemic inflammation observed in scrub typhus.

MeSH terms

  • Cells, Cultured
  • Humans
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Orientia tsutsugamushi / immunology*
  • Orientia tsutsugamushi / physiology
  • Scrub Typhus / genetics
  • Scrub Typhus / immunology*
  • Scrub Typhus / microbiology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Interferon Type I
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma