Immunologic Indicators of Clinical Progression during Canine Leishmania infantum Infection
Immunologic Indicators of Clinical Progression during Canine Leishmania infantum Infection
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DOI：
10.1128/cvi.00456-09
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发表时间：
2010-02-01
影响因子：
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通讯作者：
Petersen, Christine A.
中科院分区：
文献类型：
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作者：
Boggiatto, Paola M.;Ramer-Tait, Amanda E.;Petersen, Christine A.
在狗和人类中，婴儿利什曼原虫感染比疾病更普遍，因为感染通常不等同于临床疾病。先前的研究还表明，晚期临床内脏利什曼病的特征是抗利什曼抗体的产生增加，利什曼特异性淋巴组织增生性无反应性，γ干扰素（IFN-γ）的产生减少，伴随白细胞介素-10（IL-10）的增加。为了区分感染与进行性疾病以更好地诊断疾病，我们暂时评估了自然感染犬的体液和细胞免疫学参数。本文首次描述了对天然土著L.美国境内猎狐犬的婴儿感染。在区分感染与临床疾病时，应考虑免疫学参数的几个关键变化，包括IgG产生的急剧增加，抗原特异性外周血单核细胞增殖的进行性增加，以及IFN-γ的产生。通过增加IL-10产生和全血中寄生虫动基体DNA的一致检测来排除多症状疾病。这种临床表现和免疫失调反映了在人类患者中观察到的那些，表明这种动物模型对于测试免疫调节性抗IL-10和其他疗法将是非常有用的。
In both dogs and humans Leishmania infantum infection is more prevalent than disease, as infection often does not equate with clinical disease. Previous studies additively indicate that advanced clinical visceral leishmaniasis is characterized by increased production of anti-Leishmania antibodies, Leishmania-specific lymphoproliferative unresponsiveness, and decreased production of gamma interferon (IFN-gamma) with a concomitant increase of interleukin-10 (IL-10). In order to differentiate infection versus progressive disease for better disease prognostication, we temporally evaluated humoral and cellular immunologic parameters of naturally infected dogs. The work presented here describes for the first time the temporal immune response to natural autochthonous L. infantum infection in foxhounds within the United States. Several key changes in immunological parameters should be considered when differentiating infection versus clinical disease, including a dramatic rise in IgG production, progressive increases in antigen-specific peripheral blood mononuclear cell proliferation, and IFN-gamma production. Polysymptomatic disease is precluded by increased IL-10 production and consistent detection of parasite kinetoplast DNA in whole blood. This clinical presentation and the immuno-dysregulation mirror those observed in human patients, indicating that this animal model will be very useful for testing immunomodulatory anti-IL-10 and other therapies.