Amaral V F, Ransatto V A, Conceicão-Silva F, Molinaro E, Ferreira V, Coutinho S G, McMahon-Pratt D, Grimaldi G
Departamento de Imunologia, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Exp Parasitol. 1996 Jan;82(1):34-44. doi: 10.1006/expr.1996.0005.
As a means of assessing the usefulness of the Rhesus macaque (Macaca mulatta) as a nonhuman primate model for studying cutaneous leishmaniasis, monkeys were infected with Leishmania amazonensis. Variation in the level of susceptibility was found; however, animals inoculated with 10(8) promastigotes provided consistent results as indicated by an earlier onset and/or larger size of lesions. Three monkeys, which had recovered from skin lesions, were challenge-infected using the same parasite strain/dose; although these animals remained susceptible to homologous infection, lesion size was smaller and healed faster than in the initial infection. The immunologic features during infection were assessed. Levels of IgM and IgG antibodies to promastigote antigens rose during active infection and then declined; immunoblot analyses indicated that numerous leishmanial antigens (predominately >30 kDa) were recognized. Delayed type hypersensitivity (DTH) responses and proliferative responses (PBL) developed during active infection and/or rechallenge. Circulating peripheral T cell subpopulations varied throughout the course of infection. Initially (6-8 weeks p.i.), CD4+ T cells appear to predominate; subsequently (15-21 weeks p.i.), an increase in CD8+ T cells was observed. Pathologic analyses indicated that lesions contained amastigotes with a mononuclear infiltrate of macrophages, lymphocytes, and plasma cells, and formation of tuberculoid-type granulomas. As the progression and resolution of leishmanial infection in rhesus macaques are very similar to those observed in humans, this primate model could be employed for elucidating the mechanisms of protective immunity in cutaneous leishmaniasis.
为了评估恒河猴（猕猴）作为研究皮肤利什曼病的非人灵长类动物模型的实用性，将猴子感染亚马逊利什曼原虫。发现易感性水平存在差异；然而，接种10⁸前鞭毛体的动物提供了一致的结果，表现为病变出现更早和/或更大。三只从皮肤病变中恢复的猴子，用相同的寄生虫菌株/剂量进行再次感染；尽管这些动物仍易受同源感染，但病变大小比初次感染时更小且愈合更快。对感染期间的免疫特征进行了评估。在活跃感染期间，针对前鞭毛体抗原的IgM和IgG抗体水平上升，然后下降；免疫印迹分析表明，许多利什曼原虫抗原（主要>30 kDa）被识别。在活跃感染和/或再次攻击期间出现迟发型超敏反应（DTH）和增殖反应（PBL）。在整个感染过程中，循环外周血T细胞亚群有所变化。最初（感染后6 - 8周），CD4⁺T细胞似乎占主导；随后（感染后15 - 21周），观察到CD8⁺T细胞增加。病理分析表明，病变中含有无鞭毛体，伴有巨噬细胞、淋巴细胞和浆细胞的单核浸润，并形成结核样肉芽肿。由于恒河猴中利什曼原虫感染的进展和消退与人类中观察到的非常相似，这个灵长类动物模型可用于阐明皮肤利什曼病中保护性免疫的机制。
