IFNs and STATs in innate immunity to microorganisms.
IFNs and STATs in innate immunity to microorganisms.
复制标题
DOI：
10.1172/jci15770
复制
发表时间：
2002-05
期刊：
影响因子：
--
通讯作者：
T. Decker;Silvia Stockinger;Marina Karaghiosoff;Mathias Müller;P. Kovarik
中科院分区：
文献类型：
--
作者：
T. Decker;Silvia Stockinger;Marina Karaghiosoff;Mathias Müller;P. Kovarik
先天免疫反应源于细胞快速对抗入侵微生物的能力，而不需要抗原特异性适应。这些机制已经进化成识别常见的微生物相关分子模式，并干扰支持微生物入侵者繁殖的保守复制和生存策略。在这里，我们考虑一个细胞因子家族，IFN，对这些先天防御机制的贡献。IFN最初被认为具有阻止病毒复制的能力，这一功能确实对宿主在应对病毒感染时的生存至关重要。此外，目前已知干扰素信号在保护宿主免受细菌和其他病原体侵袭方面发挥关键作用，并有助于将适应性免疫系统介导的早期先天反应与后来的事件整合在一起。这两种公认的干扰素表现出不同的免疫学特性(1)。在人类和小鼠中，I型干扰素包括许多干扰素-α亚型和单一种类的干扰素-β。(另一种I型干扰素，干扰素-ω的免疫学影响知之甚少，这里不再讨论)。虽然在适当的条件下，所有细胞都可以产生I型IFN，但在感染期间，未成熟树突状细胞(DC)亚群在感染期间对整体干扰素产生的贡献程度突出，下文将更详细地描述。干扰素-γ是一种II型干扰素，不仅可以诱导抗病毒功能，还可以激活巨噬细胞，从而增强对单细胞微生物的先天反应。与I型IFN不同，干扰素-γ由有限数量的细胞类型产生：激活的NK细胞、激活的Th1细胞，以及在存在IL-12和IL-18的情况下，激活的DC和巨噬细胞。Th1细胞表达干扰素-γ是获得性免疫反应增强巨噬细胞天然免疫的重要环节。
Innate immune responses derive from the ability of cells to rapidly combat invading microorganisms without the requirement for an antigen-specific adaptation. These mechanisms have evolved to recognize common microbe-associated molecular patterns and to interfere with conserved replication and survival strategies that support the propagation of microbial invaders. Here, we consider the contributions of one cytokine family, the IFNs, to these innate defense mechanisms. IFNs were first recognized for their ability to impede viral replication, a function that is indeed critical for host survival in response to viral infection. In addition, IFN signaling is now known to play key roles in defending the host from bacteria and other pathogens and to help integrate early, innate responses with later events mediated by the adaptive immune system. The two recognized types of IFN exhibit distinct immunological properties (1). In humans and mice, type I IFNs include a number of IFN-α subtypes and a single species of IFN-β. (The immunological impact of another type I IFN, IFN-ω, is poorly understood and will not be considered here). While type I IFNs can be produced by all cells under appropriate conditions, a subpopulation of immature dendritic cells (DCs) that will be described in more detail below stands out for the extent of its contribution to overall IFN production during infections. IFN-γ is a type II IFN and serves not only to induce antiviral function, but also to activate macrophages, which strengthens innate responses to unicellular microorganisms (2). Unlike the type I IFNs, IFN-γ is produced by a limited number of cell types: activated NK cells, activated Th1 cells, and, in the presence of IL-12 and IL-18, activated DCs and macrophages. Expression of IFN-γ by Th1 cells provides an important link by which the adaptive immune response reinforces macrophage-based innate immunity.