Norsworthy Nilufer B, Sun Jiaren, Elnaiem Dia, Lanzaro Gregory, Soong Lynn
Department of Microbiology and Immunology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1070, USA.
Infect Immun. 2004 Mar;72(3):1240-7. doi: 10.1128/IAI.72.3.1240-1247.2004.
After transmission through the bite of female sand flies, Leishmania spp. can cause a broad spectrum of disease manifestations collectively known as leishmaniases. L. amazonensis is endemic in South America, where it causes cutaneous, diffuse cutaneous, and visceral leishmaniasis. In this study, we have provided evidence that salivary gland extracts (SGE) of Lutzomyia longipalpis enhances L. amazonensis infection. BALB/c mice infected intradermally in the ear with 10(5) metacyclic promastigotes of L. amazonensis together with SGE (equivalent to 0.5 gland) showed an early onset of disease and larger lesions that contained approximately 3-log-units more parasites than did controls. To determine the potential mechanism underlying this enhancement, we assessed cytokine production via reverse transcriptase PCR and enzyme-linked immunosorbent assay. Mice coinjected with parasites and SGE displayed higher levels of interleukin-10 (IL-10) mRNA in the ear tissues, as well as higher levels of IL-10 in supernatants of restimulated draining lymph node (LN) cells, than did controls. Flow cytometric analysis revealed high frequencies of IL-10-producing CD4(+) and CD8(+) T cells in the draining LN of mice coinjected with the parasite and SGE. In addition, we examined bone marrow derived-macrophage cultures and detected increased IL-10 but decreased nitric oxide (NO) production in cells exposed to SGE prior to infection with L. amazonensis. Together, these results imply that the sand fly saliva facilitates Leishmania evasion of the host immune system by modulating IL-10 production.
利什曼原虫通过雌性白蛉叮咬传播后，可引发一系列统称为利什曼病的疾病表现。亚马逊利什曼原虫在南美洲为地方病，可引起皮肤型、弥漫性皮肤型和内脏利什曼病。在本研究中，我们提供了证据表明长须罗蛉唾液腺提取物（SGE）可增强亚马逊利什曼原虫的感染。用10⁵个亚马逊利什曼原虫的后循环前鞭毛体与SGE（相当于0.5个腺体）皮内注射感染耳部的BALB/c小鼠，疾病发病更早，病变更大，病变中寄生虫数量比对照组多约3个对数单位。为确定这种增强作用的潜在机制，我们通过逆转录聚合酶链反应和酶联免疫吸附测定评估细胞因子的产生。与寄生虫和SGE共同注射的小鼠耳部组织中白细胞介素-10（IL-10）mRNA水平更高，再刺激的引流淋巴结（LN）细胞上清液中IL-10水平也更高。流式细胞术分析显示，与寄生虫和SGE共同注射的小鼠引流LN中产生IL-10的CD4⁺和CD8⁺T细胞频率较高。此外，我们检查了骨髓来源的巨噬细胞培养物，发现在用亚马逊利什曼原虫感染之前暴露于SGE的细胞中IL-10增加但一氧化氮（NO）产生减少。总之，这些结果表明白蛉唾液通过调节IL-10的产生促进利什曼原虫逃避宿主免疫系统。
