Induction of IFN-alphabeta enables Listeria monocytogenes to suppress macrophage activation by IFN-gamma.
Induction of IFN-alphabeta enables Listeria monocytogenes to suppress macrophage activation by IFN-gamma.
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DOI：
10.1084/jem.20091746
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发表时间：
2010-02-15
期刊：
影响因子：
--
通讯作者：
Lenz LL
中科院分区：
文献类型：
--
作者：
Rayamajhi M;Humann J;Penheiter K;Andreasen K;Lenz LL
I型干扰素（IFN; IFN-αβ）的产生增加宿主对单核增生李斯特菌的易感性，而II型干扰素（IFN-γ）激活巨噬细胞抵抗感染。我们发现，IFN-αβ和IFN-γ的这些相反的免疫作用是由于各自的信号通路之间的串扰而发生的。我们发现，由于IFN-γ受体（IFNGR）下调，单核增生乳杆菌感染的培养巨噬细胞对IFN-γ治疗难以耐受。产生这些作用的可溶性因子被鉴定为宿主IFN-αβ。因此，在IFN-αβ -应答小鼠全身感染过程中，巨噬细胞和树突状细胞（dc）的IFNGR1表达降低，对IFN-γ的反应性降低。此外，缺乏IFN-αβ受体（IFNAR - / -）的小鼠对单核增生乳杆菌的抗性增加与巨噬细胞和dc中IFN-γ依赖性激活标记物的表达增加相关，并通过消耗IFN-γ而逆转。因此，在细菌感染和其他刺激下产生的IFN-αβ通过下调IFNGR拮抗宿主对IFN-γ的反应。这种串扰允许IFN-αβ型免疫反应的优先化，并可能有助于IFN-β在治疗炎性疾病（如多发性硬化症）中的有益作用。
Production of type I interferon (IFN; IFN-αβ) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-γ) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-αβ and IFN-γ occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-γ treatment as a result of down-regulation of the IFN-γ receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-αβ. Accordingly, macrophages and dendritic cells (DCs) showed reduced IFNGR1 expression and reduced responsiveness to IFN-γ during systemic infection of IFN-αβ–responsive mice. Furthermore, the increased resistance of mice lacking the IFN-αβ receptor (IFNAR−/−) to L. monocytogenes correlated with increased expression of IFN-γ–dependent activation markers by macrophages and DCs and was reversed by depletion of IFN-γ. Thus, IFN-αβ produced in response to bacterial infection and other stimuli antagonizes the host response to IFN-γ by down-regulating the IFNGR. Such cross talk permits prioritization of IFN-αβ–type immune responses and may contribute to the beneficial effects of IFN-β in treatment of inflammatory diseases such as multiple sclerosis.
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影响因子：
4.4
作者：
Nagabhushanam, V;Solache, A;Ernst, JD
通讯作者：
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DOI：
10.1165/ajrcmb.20.3.3252
发表时间：
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影响因子：
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