Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue
Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue
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DOI：
10.1128/iai.01540-15
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发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Jutila, Mark A.
中科院分区：
文献类型：
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作者：
Hedges, Jodi F.;Robison, Amanda;Jutila, Mark A.
贝氏柯克斯体是一种胞内病原体，是Q热的病原体。γ-干扰素（IFN-γ）是保护宿主免受感染的关键，但I型IFN在C.尚未确定伯氏体感染。I型干扰素支持宿主对相关病原体嗜肺军团菌的保护作用，我们假设它在C.贝氏体感染与我们的预测相反，IFN-α受体缺陷（IFNAR（-/-））小鼠免受C。Burnetii引起的感染。因此，I型IFN在C.贝氏体感染与L.嗜肺菌用双链RNA模拟物处理的小鼠受到保护免受C. Burnetii通过IFNAR非依赖性途径诱导的体重减轻。我们接下来用重组IFN-α（rIFN-α）治疗小鼠。当在感染期间通过腹膜内途径注射rIFN-α时，疾病引起的体重减轻加剧。通过这种途径接受rIFN-α的小鼠在支气管肺泡灌洗液中抑制了白细胞介素1 β（IL-1 β）的表达。然而，当rIFN-α被递送到肺时，所有组织中的细菌复制都减少了。因此，I型IFN在肺中的存在保护免受感染，但当递送至外周时，I型IFN可能通过抑制炎性细胞因子而增强疾病。为了更好地表征C.贝氏梭菌的脂多糖（LPS）刺激后，我们评估了人巨噬细胞IFN-β转录物的表达。伯内特氏菌理解C.贝氏体感染将有助于发现新的疗法，这些疗法可能是目前抗生素治疗的替代或补充。
Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-gamma) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, and we hypothesized that it would be similarly protective in C. burnetii infection. In contrast to our prediction, IFN-alpha receptor-deficient (IFNAR(-/-)) mice were protected from C. burnetii-induced infection. Therefore, the role of type I IFN in C. burnetii infection was distinct from that in L. pneumophila. Mice treated with a double-stranded-RNA mimetic were protected from C. burnetii-induced weight loss through an IFNAR-independent pathway. We next treated mice with recombinant IFN-alpha (rIFN-alpha). When rIFN-alpha was injected by the intraperitoneal route during infection, disease-induced weight loss was exacerbated. Mice that received rIFN-alpha by this route had dampened interleukin 1 beta (IL-1 beta) expression in bronchoalveolar lavage fluids. However, when rIFN-alpha was delivered to the lung, bacterial replication was decreased in all tissues. Thus, the presence of type I IFN in the lung protected from infection, but when delivered to the periphery, type I IFN enhanced disease, potentially by dampening inflammatory cytokines. To better characterize the capacity for type I IFN induction by C. burnetii, we assessed expression of IFN-beta transcripts by human macrophages following stimulation with lipopolysaccharide (LPS) from C. burnetii. Understanding innate responses in C. burnetii infection will support the discovery of novel therapies that may be alternative or complementary to the current antibiotic treatment.