Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
PLoS Negl Trop Dis. 2012;6(6):e1667. doi: 10.1371/journal.pntd.0001667. Epub 2012 Jun 5.
Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models.
We studied susceptibility to L. tropica, using BALB/c-c-STS/A (CcS/Dem) recombinant congenic (RC) strains, which differ greatly in susceptibility to L. major. Mice were infected with L. tropica and skin lesions, cytokine and chemokine levels in serum, and parasite numbers in organs were measured.
Females of BALB/c and several RC strains developed skin lesions. In some strains parasites visceralized and were detected in spleen and liver. Importantly, the strain distribution pattern of symptoms caused by L. tropica was different from that observed after L. major infection. Moreover, sex differently influenced infection with L. tropica and L. major. L. major-infected males exhibited either higher or similar skin pathology as females, whereas L. tropica-infected females were more susceptible than males. The majority of L. tropica-infected strains exhibited increased levels of chemokines CCL2, CCL3 and CCL5. CcS-16 females, which developed the largest lesions, exhibited a unique systemic chemokine reaction, characterized by additional transient early peaks of CCL3 and CCL5, which were not present in CcS-16 males nor in any other strain.
Comparison of L. tropica and L. major infections indicates that the strain patterns of response are species-specific, with different sex effects and largely different host susceptibility genes.
利什曼病是一种由原生动物利什曼原虫属寄生虫引起的疾病。最近才认识到利什曼热带原虫经常参与人类利什曼病。与 L. major 一样，L. tropica 在人类中引起皮肤利什曼病，但也可以内脏化并引起全身性疾病。宿主基因型与疾病表现之间的关系尚不清楚，因为没有合适的动物模型。
我们使用 BALB/c-c-STS/A（CcS/Dem）重组近交系（RC）品系研究了对 L. tropica 的易感性，这些品系在对 L. major 的易感性上有很大差异。用 L. tropica 感染小鼠，测量皮肤损伤、血清细胞因子和趋化因子水平以及器官中的寄生虫数量。
BALB/c 和几个 RC 品系的雌性出现皮肤损伤。在一些品系中，寄生虫内脏化并在脾脏和肝脏中被检测到。重要的是，L. tropica 引起的症状的品系分布模式与 L. major 感染后的观察结果不同。此外，性别对 L. tropica 和 L. major 的感染有不同的影响。L. major 感染的雄性表现出与雌性相似或更高的皮肤病理学，而 L. tropica 感染的雌性比雄性更容易感染。大多数 L. tropica 感染的菌株表现出趋化因子 CCL2、CCL3 和 CCL5 水平升高。出现最大损伤的 CcS-16 雌性表现出独特的全身趋化因子反应，其特征是 CCL3 和 CCL5 的早期短暂峰值增加，而在 CcS-16 雄性和任何其他品系中都不存在。
L. tropica 和 L. major 感染的比较表明，反应的品系模式是特定于物种的，具有不同的性别效应和很大程度上不同的宿主易感性基因。
