IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12
IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12
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DOI：
10.4049/jimmunol.173.3.1887
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发表时间：
2004-08-01
影响因子：
4.4
通讯作者：
Hunter, CA
中科院分区：
文献类型：
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作者：
Lieberman, LA;Cardillo, F;Hunter, CA
IL-23和IL-12是异二聚体细胞因子，它们共享p40亚基，但具有独特的第二亚基IL-23p19和IL-12p35。由于p40是产生对刚地弓形虫产生抗性所需的Th1型应答所必需的，因此进行了研究以评估IL-23在对该病原体的抗性中的作用。在感染弓形虫的小鼠中检测到IL-23水平升高，用弓形虫病原体体外刺激树突状细胞导致该细胞因子mRNA水平升高。为了研究IL-23在抵抗弓形虫中的作用，我们感染了缺乏p40亚基（IL-12和IL-23共有）的小鼠和缺乏IL-12 p35 （IL-12特异性）的小鼠，并比较了它们的反应。这些研究表明，p40（-/-）小鼠迅速死于弓形虫病，而p35（-/-）小鼠表现出增强的抵抗力，尽管它们最终死于这种感染。此外，给感染弓形虫的p40（-/-）小鼠注射IL-23可减少寄生虫负担并增强抗性。然而，经IL-23处理的p35（-/-）小鼠或p40（-/-）小鼠的抗性增强与ifn - γ产生的增加无关。当IL-23p19（-/-）小鼠感染弓形虫后，这些小鼠产生正常的T细胞反应，并在与野生型小鼠相同的程度上控制寄生虫复制。总之，这些研究表明，IL-12，而不是IL-23，在对弓形虫病的抗性中起主导作用，但是，在缺乏IL-12的情况下，IL-23可以提供有限的抵抗这种感染的机制。
IL-23 and IL-12 are heterodimeric cytokines which share the p40 subunit, but which have unique second subunits, IL-23p19 and IL-12p35. Since p40 is required for the development of the Th1 type response necessary for resistance to Toxoplasma gondii, studies were performed to assess the role of IL-23 in resistance to this pathogen. Increased levels of IL-23 were detected in mice infected with T. gondii and in vitro stimulation of dendritic cells with this pathogen resulted in increased levels of mRNA for this cytokine. To address the role of IL-23 in resistance to T. gondii, mice lacking the p40 subunit (common to IL-12 and IL-23) and mice that lack IL-12 p35 (specific for IL-12) were infected and their responses were compared. These studies revealed that p40(-/-) mice rapidly succumbed to toxoplasmosis, while p35(-/-) mice displayed enhanced resistance though they eventually succumbed to this infection. In addition, the administration of IL-23 to p40(-/-) mice infected with T. gondii resulted in a decreased parasite burden and enhanced resistance. However, the enhanced resistance of p35(-/-) mice or p40(-/-) mice treated with IL-23 was not associated with increased production of IFN-gamma. When IL-23p19(-/-) mice were infected with T. gondii these mice developed normal T cell responses and controlled parasite replication to the same extent as wild-type mice. Together, these studies indicate that IL-12, not IL-23, plays a dominant role in resistance to toxoplasmosis but, in the absence of IL-12, IL-23 can provide a limited mechanism of resistance to this infection.