Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost importance. Here we show that type I interferon (IFN) signaling protects against lung infection with K. pneumoniae by launching bacterial growth-controlling interactions between alveolar macrophages and natural killer (NK) cells. Type I IFNs are important but disparate and incompletely understood regulators of defense against bacterial infections. Type I IFN receptor 1 (Ifnar1)-deficient mice infected with K. pneumoniae failed to activate NK cell-derived IFN-γ production. IFN-γ was required for bactericidal action and the production of the NK cell response-amplifying IL-12 and CXCL10 by alveolar macrophages. Bacterial clearance and NK cell IFN-γ were rescued in Ifnar1-deficient hosts by Ifnar1-proficient NK cells. Consistently, type I IFN signaling in myeloid cells including alveolar macrophages, monocytes and neutrophils was dispensable for host defense and IFN-γ activation. The failure of Ifnar1-deficient hosts to initiate a defense-promoting crosstalk between alveolar macrophages and NK cell was circumvented by administration of exogenous IFN-γ which restored endogenous IFN-γ production and restricted bacterial growth. These data identify NK cell-intrinsic type I IFN signaling as essential driver of K. pneumoniae clearance, and reveal specific targets for future therapeutic exploitations.

由于最近分离出了多药耐药菌株，肺炎克雷伯菌是医院内肺炎的重要原因，也是令人震惊的病原体。了解协调K的免疫反应。宿主清除肺炎至关重要。在这里，我们表明，I型干扰素（IFN）信号防止肺部感染与ķ。通过在肺泡巨噬细胞和自然杀伤（NK）细胞之间启动细菌生长控制相互作用来控制肺炎。I型干扰素很重要，但是对细菌感染防御的调节剂却是完全不同的，而且还没有完全了解。I型干扰素受体1（IFNAR1）缺陷小鼠感染ķ。肺炎未能激活NK细胞衍生的IFN-γ的产生。肺泡巨噬细胞的杀菌作用和NK细胞应答放大型IL-12和CXCL10的产生需要IFN-γ。Ifnar1缺陷型NK细胞在Ifnar1缺陷型宿主中拯救细菌清除率和NK细胞IFN-γ 。一致地，包括肺泡巨噬细胞，单核细胞和中性粒细胞在内的髓样细胞中的I型IFN信号传导对于宿主防御和IFN-γ激活是必不可少的。Ifnar1的失败通过给予外源性IFN-γ来规避缺乏宿主启动肺泡巨噬细胞和NK细胞之间的防御反应，从而恢复内源性IFN-γ的产生并限制细菌的生长。这些数据将NK细胞本征I型IFN信号转导为K的重要驱动力。清除肺炎，并揭示未来治疗用途的特定目标。