Lack of IFN-g signaling leads to enhanced susceptibility to eschar-associated scrub typhus in mice

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B564
Abstract ID: 4531

Presenting Author:
Yuejin Liang , Assistant Professor at Univ. of Texas Med. Br., Galveston

Abstract:

Scrub typhus is an infectious disease caused by the bacteria Orientia tsutsugamushi (Ot). Severe infection can lead to organ failure and hemorrhage, resulting in fatality without proper treatment. The mechanism of how the host innate immune system responds to this infection remains elusive. By using an intradermal (i.d.) inoculation mouse model, we found that dendritic cells (DCs) and macrophages (MФ) were the major cell subsets responsible for bacterial uptake in dermis and dissemination into draining lymph nodes (dLN), leading to a systemic infection. This process was dependent on the chemokine receptor CCR7. Interferons (IFNs) are known to play a crucial role in microbial infection defense. Our data showed that the levels of IFNs increased significantly in the skin and lymph nodes after infection. To investigate the role of IFNs in Ot infection, we i.d. infected Ifnar1- or Ifngr-deficient mice and found that the lack of IFN-γ, but not IFN-I signaling, resulted in visible skin eschar lesions, higher bacterial burdens in dLN, exacerbated systemic infection, and animal lethality. Our in vitro study demonstrated that IFN-γ restricted bacterial growth in DCs and MФ, suggesting that IFN-γ may inhibit bacterial dissemination in vivo by signaling on bacteria-carrying myeloid cells. Overall, our findings reveal a Trojan horse mechanism of bacterial transmission and highlight the crucial role of IFN-γ signaling in host protection against scrub typhus.