Leptak C L, McKerrow J H
Department of Microbiology and Immunology, University of California-San Francisco 94143, USA.
J Immunol. 1997 Jan 1;158(1):301-7.
Granulomatous inflammation is key to the pathogenesis of many infectious diseases, including hepatic schistosomiasis. The granulomas that form around schistosome eggs trapped in the liver of infected hosts were thought to be induced primarily, if not exclusively, by egg Ags. We now show that the maturation of adult worms, before the production of eggs, primes local immune responses key to granuloma formation. When parasite eggs are injected into the livers of naive animals, only a minimal, nongranulomatous, inflammatory response results. However, if eggs are injected into the livers of mice previously infected with single-sex adult worms, granuloma formation is restored. Granuloma formation is also restored if mice are presensitized with adult worm homogenates or with eggs themselves before egg injection into the liver. These sensitization studies confirm that an Ag or Ags are shared between different stages of the schistosome life cycle and that immune priming by these Ag(s) is necessary for hepatic granuloma formation. Models of infection that isolate the effects of worms from those of eggs confirm that each of these life cycle stages induces a unique pattern of cytokine expression. Hepatic expression of TNF-alpha, a major cytokine signal for granuloma formation, is a reaction to adult worms, not eggs. TNF-alpha may mediate immune priming necessary for granuloma development since injection of purified TNF-alpha alone restores formation of granulomas in the livers of naive mice injected with eggs.
肉芽肿性炎症是包括肝血吸虫病在内的许多传染病发病机制的关键。人们认为，被困在受感染宿主肝脏中的血吸虫卵周围形成的肉芽肿主要（如果不是唯一）由虫卵抗原诱导。我们现在表明，成虫在产卵之前的成熟会引发对肉芽肿形成至关重要的局部免疫反应。当将寄生虫卵注射到未感染的动物肝脏中时，只会产生最小程度的、非肉芽肿性的炎症反应。然而，如果将虫卵注射到先前感染过单性成虫的小鼠肝脏中，肉芽肿形成得以恢复。如果在将虫卵注射到肝脏之前，先用成虫匀浆或虫卵本身对小鼠进行预致敏，肉芽肿形成也会恢复。这些致敏研究证实，血吸虫生命周期的不同阶段之间存在一种或多种共享抗原，并且这些抗原引发的免疫致敏对于肝脏肉芽肿形成是必要的。将蠕虫和虫卵的作用分开的感染模型证实，生命周期的每个阶段都会诱导独特的细胞因子表达模式。肿瘤坏死因子-α（TNF-α）是肉芽肿形成的主要细胞因子信号，其在肝脏中的表达是对成虫而非虫卵的反应。TNF-α可能介导肉芽肿发育所需的免疫致敏，因为单独注射纯化的TNF-α可恢复在注射虫卵的未感染小鼠肝脏中肉芽肿的形成。
