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.

肺炎克雷伯菌是院内肺炎的重要病因，由于最近分离出多重耐药菌株，因此也是一种令人担忧的病原体。了解协调免疫反应K .宿主对肺炎支原体的清除至关重要。在这里，我们展示了 I 型干扰素 (IFN) 信号传导可防止肺炎克雷伯菌肺部感染。通过启动肺泡巨噬细胞和自然杀伤 (NK) 细胞之间的细菌生长控制相互作用来抑制肺炎链球菌。 I 型干扰素很重要，但它们是不同且不完全了解的细菌感染防御调节剂。 I 型 IFN 受体 1 ( Ifnar1 ) 缺陷型小鼠感染K 菌。肺炎链球菌未能激活 NK 细胞衍生的 IFN-γ 产生。杀菌作用和肺泡巨噬细胞产生 NK 细胞反应放大 IL-12 和 CXCL10 需要 IFN-γ。在Ifnar1缺陷的宿主中， Ifnar1熟练的 NK 细胞可以挽救细菌清除和 NK 细胞 IFN-γ。一致地，骨髓细胞（包括肺泡巨噬细胞、单核细胞和中性粒细胞）中的 I 型 IFN 信号传导对于宿主防御和 IFN-γ 激活来说是可有可无的。 Ifnar1缺陷型宿主未能启动肺泡巨噬细胞和NK细胞之间促进防御的串扰，这可以通过施用外源性IFN-γ来避免，从而恢复内源性IFN-γ的产生并限制细菌生长。这些数据表明 NK 细胞固有的 I 型 IFN 信号传导是K的重要驱动因素。肺炎球菌清除，并揭示未来治疗开发的具体目标。