Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria
Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria
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DOI：
10.4049/jimmunol.178.5.3126
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Teti, Giuseppe
中科院分区：
文献类型：
--
作者：
Mancuso, Giuseppe;Midiri, Angelina;Teti, Giuseppe
已知宿主细胞在接触保守的细菌产物后可以产生I型干扰素(干扰素-α-β)，但这种反应对细菌感染结局的功能后果尚不完全清楚。我们在这项研究中表明，干扰素-β信号对于宿主对不同细菌的防御至关重要，这些细菌包括B组链球菌(GBS)、肺炎球菌和大肠杆菌。作为对GBS攻击的响应，大多数缺乏干扰素-α-βR或干扰素-β的小鼠死于无限制的菌血症，而所有野生型对照小鼠都存活了下来。干扰素-α-βR缺乏的影响是显著的，死亡率超过了干扰素-α-R缺陷小鼠。缺乏干扰素-α-βR和干扰素-γR的动物表现出相加致死性，这表明这两种类型的干扰素在宿主防御中具有互补和非多余的作用。巨噬细胞暴露于GBS后，干扰素-α-β的分泌增加。此外，在缺乏干扰素-αβ信号的情况下，观察到活细菌或纯化的内毒素刺激巨噬细胞后，巨噬细胞产生的干扰素-γ、一氧化氮和肿瘤坏死因子-α显著减少。总而言之，我们的数据证明了干扰素-αβ在增强巨噬细胞反应和宿主对细菌病原体的抵抗力方面的新的基本功能。这些数据可能有助于设计治疗细菌感染的替代策略。
It is known that host cells can produce type I IFNs (IFN-alpha beta) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-alpha beta signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-alpha beta R or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alpha beta R deficiency was marked, with mortality surpassing that seen in IFN-gamma R-deficient mice. Animals lacking both IFN-alpha beta R and IFN-gamma R displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased procluction of IFN-alpha beta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alpha beta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alpha beta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.