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Published on: March 12, 2015
Orientia tsutsugamushi, the causative agent of scrub typhus, induces an inflammatory program in human macrophages
Wiwit Tantibhedhyangkul1, Amira Ben Amara, Julien Textoris
1Aix-Marseille Université, URMITE, UMR CNRS, IRD, Inserm, France. wiwit167@yahoo.co.th
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.
Insights
Orientia tsutsugamushi, the cause of scrub typhus, replicates in macrophages and triggers inflammatory responses. Interferon-gamma partially inhibits bacterial growth, suggesting a role in controlling infection.
Area of Science:
- Infectious Diseases
- Cellular Microbiology
- Immunology
Background:
- Scrub typhus is a severe illness caused by Orientia tsutsugamushi.
- This bacterium primarily targets endothelial cells.
- Myeloid cell interactions are implicated in O. tsutsugamushi pathogenesis.
Purpose of the Study:
- To investigate the interaction between O. tsutsugamushi and human macrophages.
- To elucidate the host immune response triggered by O. tsutsugamushi infection.
- To explore the potential role of interferon-gamma in controlling scrub typhus.
Main Methods:
- Macrophages were infected with O. tsutsugamushi.
- Gene expression and cytokine release were analyzed.
- The effect of exogenous interferon-gamma on bacterial replication was assessed.
Main Results:
- O. tsutsugamushi replicated within human monocyte-derived macrophages.
- Infection induced type I interferon, inflammation, and apoptosis-related genes, along with TNF and IL-1β release.
- O. tsutsugamushi promoted an M1 macrophage polarization.
- Bacterial viability was essential for type I interferon and inflammatory responses.
- Interferon-gamma partially inhibited O. tsutsugamushi replication.
Conclusions:
- O. tsutsugamushi infection of macrophages elicits significant immune responses.
- The observed inflammatory response may contribute to the systemic inflammation in scrub typhus.
- Interferon-gamma shows potential as a therapeutic modulator against O. tsutsugamushi.
