CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis

CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis
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DOI:
10.4049/jimmunol.168.11.5730
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发表时间:
2002-06-01
影响因子:
4.4
通讯作者:
Austen, KF
Austen, KF
中科院分区:
医学2区
文献类型:
--
作者:
Gurish, MF;Humbles, A;Austen, KF

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CCR 3结合至少七种不同的CC趋化因子,并在嗜酸性粒细胞、肥大细胞(MC)和产生涉及粘膜免疫应答的细胞因子的Th细胞(Th 2)的子集上表达。使用具有CCR 3(-/-)的靶向破坏的小鼠和它们的+/+同窝小鼠,我们研究了CCR 3在旋毛虫感染后小鼠组织嗜酸性粒细胞增多和MC增生的扩增中的作用。在CCR 3-/-小鼠中,嗜酸性粒细胞在感染后不被募集到空肠粘膜,并且不存在于邻近包囊幼虫的骨骼肌中。此外,骨骼肌中包囊的数量增加,包囊幼虫表现出坏死的频率降低。CCR 3(-/-)小鼠在空肠和盲肠中表现出预期的MC增生,并以正常速率从小肠排斥蠕虫。本研究与MC(成虫排出)和嗜酸性粒细胞(对幼虫的毒性)在蠕虫T. spiralis,并定义了嗜酸性粒细胞中CCR 3的基本要求,但不是MC募集到组织中。
The CCR3 binds at least seven different CC chemokines and is expressed on eosinophils, mast cells (MC), and a subset of Th cells (Th2) that generate cytokines implicated in mucosal immune responses. Using mice with a targeted disruption of CCR3 (CCR3(-/-)) and their +/+ littermates, we investigated the role of CCR3 in the amplification of tissue eosinophilia and MC hyperplasia in the mouse after infection with Trichinella spiralis. In CCR3-/- mice, eosinophils are not recruited to the jejunal mucosa after infection and are not present in the skeletal muscle adjacent to encysting larvae. In addition, the number of cysts in the skeletal muscle is increased and the frequency of encysted larvae exhibiting necrosis is reduced. The CCR3(-/-) mice exhibit the expected MC hyperplasia in the jejunum and caecum and reject the adult worms from the small intestine at a normal rate. This study is consistent with distinct functions for MC (adult worm expulsion) and eosinophils (toxicity to larvae) in immunity to a helminth, T. spiralis, and defines the essential requirement for CCR3 in eosinophil, but not MC recruitment to tissues.