Cunha Jurema M, Abbehusen Melissa, Suarez Martha, Valenzuela Jesus, Teixeira Clarissa R, Brodskyn Cláudia I
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Acta Trop. 2018 Jan;177:164-170. doi: 10.1016/j.actatropica.2017.10.009. Epub 2017 Oct 14.
Leishmania is transmitted in the presence of sand fly saliva. Protective immunity generated by saliva has encouraged identification of a vector salivary-based vaccine. Previous studies have shown that immunization with LJM11, a salivary protein from Lutzomyia longipalpis, is able to induce a Th1 immune response and protect mice against bites of Leishmania major-infected Lutzomyia longipalpis. Here, we further investigate if immunization with LJM11 recombinant protein is able to confer cross-protection against infection with Leishmania braziliensis associated with salivary gland sonicate (SGS) from Lutzomyia intermedia or Lu. longipalpis. Mice immunized with LJM11 protein exhibited an increased production of anti-LJM11 IgG, IgG1 and IgG2a and a DTH response characterized by an inflammatory infiltrate with the presence of CD4 IFN-γ T cells. LJM11-immunized mice were intradermally infected in the ear with L. braziliensis in the presence of Lu. longipalpis or Lu. intermedia SGS. A significant reduction of parasite numbers in the ear and lymph node in the group challenged with L. braziliensis plus Lu. longipalpis SGS was observed, but not when the challenge was performed with L. braziliensis plus Lu. intermedia SGS. A higher specific production of IFN-γ and absence of IL-10 by lymph node cells were only observed in LJM11 immunized mice after infection. After two weeks, a similar frequency of CD4 IFN-γ T cells was detected in LJM11 and BSA groups challenged with L. braziliensis plus Lu. longipalpis SGS, suggesting that early events possibly triggered by immunization are essential for protection against Leishmania infection. Our findings support the specificity of saliva-mediated immune responses and reinforce the importance of identifying cross-protective salivary antigens.
利什曼原虫在白蛉唾液存在的情况下传播。唾液产生的保护性免疫促使人们去鉴定基于媒介唾液的疫苗。先前的研究表明，用来自长须罗蛉的唾液蛋白LJM11进行免疫能够诱导Th1免疫反应，并保护小鼠免受感染杜氏利什曼原虫的长须罗蛉叮咬。在此，我们进一步研究用LJM11重组蛋白进行免疫是否能够对来自中间罗蛉或长须罗蛉的唾液腺超声提取物（SGS）相关的巴西利什曼原虫感染提供交叉保护。用LJM11蛋白免疫的小鼠表现出抗LJM11 IgG、IgG1和IgG2a的产生增加，以及以存在CD4 IFN-γ T细胞的炎性浸润为特征的迟发型超敏反应（DTH）。用LJM11免疫的小鼠在长须罗蛉或中间罗蛉SGS存在的情况下，在耳部皮内感染巴西利什曼原虫。在用巴西利什曼原虫加长沙罗蛉SGS攻击的组中，观察到耳部和淋巴结中的寄生虫数量显著减少，但在用巴西利什曼原虫加中间罗蛉SGS进行攻击时则未观察到。仅在感染后的LJM11免疫小鼠中观察到淋巴结细胞产生更高的IFN-γ特异性产物且无IL-10。两周后，在用巴西利什曼原虫加长沙罗蛉SGS攻击的LJM11和牛血清白蛋白（BSA）组中检测到相似频率的CD4 IFN-γ T细胞，这表明免疫可能触发的早期事件对于抵抗利什曼原虫感染至关重要。我们的研究结果支持唾液介导的免疫反应的特异性，并强化了鉴定交叉保护性唾液抗原的重要性。
