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在BALB/c、BALB/c裸鼠和C57BL/6小鼠中观察到感染亚马逊利什曼原虫(Leishmania (L.) amazonensis)的不同病程。

Distinct courses of infection with Leishmania (L.) amazonensis are observed in BALB/c, BALB/c nude and C57BL/6 mice.

作者信息

Velasquez Leonardo G, Galuppo Mariana K, DE Rezende Eloiza, Brandão Wesley N, Peron Jean Pierre, Uliana Silvia R B, Duarte Maria Irma, Stolf Beatriz S

机构信息

Department of Parasitology,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.

Department of Immunology,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.

出版信息

Parasitology. 2016 May;143(6):692-703. doi: 10.1017/S003118201600024X. Epub 2016 Feb 19.

Abstract

Leishmania (L.) amazonensis [L. (L.) amazonensis] is widely distributed in Brazil and its symptomatic infections usually lead to few localized lesions and sometimes to diffuse cutaneous form, with nodules throughout the body, anergy to parasite antigens and poor therapeutic response. The variability of these manifestations draws attention to the need for studies on the pathophysiology of infection by this species. In this study, we analysed the course and immunological aspects of L. (L.) amazonensis infection in BALB/c and C57BL/6 strains, both susceptible, but displaying different clinical courses, and athymic BALB/c nude, to illustrate the role of T cell dependent responses. We analysed footpad thickness and parasite burden by in vivo imaging. Furthermore, we evaluated the cellular profile and cytokine production in lymph nodes and the inflammatory infiltrates of lesions. Nude mice showed delayed lesion development and less inflammatory cells in lesions, but higher parasite burden than BALB/c and C57BL/6. BALB/c and C57BL/6 mice had similar parasite burdens, lesion sizes and infiltrates until 6 weeks after infection, and after that C57BL/6 mice controlled the infection. Small differences in parasite numbers were observed in C57BL/6 macrophages in vitro, indicating that in vivo milieu accounts for most differences in infection. We believe our results shed light on the role of host immune system in the course of L. (L.) amazonensis infection by comparing three mouse strains that differ in parasitaemia and inflammatory cells.

摘要

亚马逊利什曼原虫[亚马逊利什曼原虫(Leishmania (L.) amazonensis)]广泛分布于巴西,其有症状感染通常导致少数局部病变,有时会发展为全身出现结节的弥漫性皮肤型,对寄生虫抗原有无反应性,且治疗反应不佳。这些表现的变异性促使人们关注对该物种感染病理生理学进行研究的必要性。在本研究中,我们分析了易感但临床病程不同的BALB/c和C57BL/6品系以及无胸腺BALB/c裸鼠体内亚马逊利什曼原虫感染的过程和免疫学方面,以阐明T细胞依赖性反应的作用。我们通过体内成像分析了足垫厚度和寄生虫负荷。此外,我们评估了淋巴结中的细胞谱和细胞因子产生以及病变部位的炎性浸润。裸鼠的病变发展延迟,病变中的炎性细胞较少,但寄生虫负荷高于BALB/c和C57BL/6小鼠。在感染后6周内,BALB/c和C57BL/6小鼠的寄生虫负荷、病变大小和浸润情况相似,之后C57BL/6小鼠控制了感染。在体外观察到C57BL/6巨噬细胞中的寄生虫数量存在微小差异,这表明体内环境是感染差异的主要原因。我们相信,通过比较三种在寄生虫血症和炎性细胞方面存在差异的小鼠品系,我们的结果揭示了宿主免疫系统在亚马逊利什曼原虫感染过程中的作用。

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