Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection.
Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection.
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DOI：
10.1084/jem.20021183
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发表时间：
2002-11-04
期刊：
影响因子：
--
通讯作者：
Sher A
中科院分区：
文献类型：
--
作者：
Aliberti J;Serhan C;Sher A
白细胞介素（IL）-12的产生是产生干扰素（IFN）-γ依赖的弓形虫抗性的关键。然而，当这种反应失调时，例如在不存在IL-10的情况下发生时，所产生的不受控制的炎症可能对宿主具有致命的后果。最近，我们证明脂氧素（LX）A4，一种依赖于5-脂氧合酶（LO）生物合成的类花生酸介质，对T.弓形虫提取物我们现在正式建立了该途径在由活T细胞诱导的IL-12产生的系统控制中的生理相关性。弓形虫感染，并证明其功能不同于IL-10。因此，T.暴露于刚地氏菌的野生型动物在慢性感染开始时产生高水平的血清LXA 4，但5-LO缺陷型动物没有。此外，与野生型小鼠相比，5-LO−/−小鼠在同一时期死亡，表现出明显的脑炎。5-LO−/−动物死亡率的增加也与IL-12和IFN-γ的显著升高相关，并且通过给予稳定的LXA 4类似物完全防止。总之，这些发现表明了一种新的途径，涉及诱导宿主LX在体内调节微生物感染期间的促炎反应。
The production of interleukin (IL)-12 is critical for the development of interferon (IFN)-γ–dependent resistance to Toxoplasma gondii. Nevertheless, when this response is dysregulated, such as occurs in the absence of IL-10, the uncontrolled inflammation that results can have lethal consequences for the host. Recently, we demonstrated that lipoxin (LX)A4, an eicosanoid mediator that depends on 5-lipoxygenase (LO) for its biosynthesis, exerts a regulatory role on dendritic cell IL-12 production triggered artificially by a T. gondii extract. We now formally establish the physiological relevance of this pathway in the systemic control of IL-12 production induced by live T. gondii infection and demonstrate its function to be distinct from that of IL-10. Thus, T. gondii–exposed wild-type, but not 5-LO–deficient animals, produced high levels of serum LXA4 beginning at the onset of chronic infection. Moreover, 5-LO−/−, in contrast to wild-type mice, succumbed during the same period displaying a marked encephalitis. The increased mortality of the 5-LO−/− animals was also associated with significant elevations of IL-12 and IFN-γ and was completely prevented by the administration of a stable LXA4 analogue. Together, these findings demonstrate a new pathway involving the induction of host LXs for the in vivo regulation of proinflammatory responses during microbial infection.
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可诱导的一氧化氮对于对持续性的宿主控制，但不能用细胞内病原体弓形虫造成的急性感染。
影响因子：
15.3
作者：
Scharton-Kersten, T M;Yap, G;Magram, J;Sher, A
通讯作者：
Sher, A
影响因子：
30.5
作者：
Aliberti, J;Hieny, S;Sher, A
通讯作者：
Sher, A
影响因子：
2.9
作者：
SERHAN, CN;MADDOX, JF;MADARA, JL
通讯作者：
MADARA, JL
影响因子：
2.9
作者：
Fiore, S;Serhan, CN
通讯作者：
Serhan, CN
影响因子：
3.1
作者：
Deckert, M;Soltek, S;Schlüter, D
通讯作者：
Schlüter, D