Immunization with LJM11 salivary protein protects against infection with Leishmania braziliensis in the presence of Lutzomyia longipalpis saliva

Immunization with LJM11 salivary protein protects against infection with Leishmania braziliensis in the presence of Lutzomyia longipalpis saliva
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DOI:
10.1016/j.actatropica.2017.10.009
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发表时间:
2018-01-01
期刊:
影响因子:
2.7
通讯作者:
Brodskyn, Claudia I.
Brodskyn, Claudia I.
中科院分区:
医学2区
文献类型:
--
作者:
Cunha, Jurema M.;Abbehusen, Melissa;Brodskyn, Claudia I.

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利什曼原虫在沙蝇唾液中传播。唾液产生的保护性免疫促进了基于唾液的载体疫苗的鉴定。先前的研究表明,用长鼻Lutzomyia long - palpis唾液蛋白LJM11免疫能够诱导Th1免疫反应,并保护小鼠免受利什曼原虫感染的长鼻Lutzomyia叮咬。在这里,我们进一步研究了LJM11重组蛋白免疫是否能够赋予巴西利什曼原虫(Leishmania)与中间卢氏菌(Lutzomyia)或卢氏菌(Lu)的涎腺声索(SGS)相关感染的交叉保护。longipalpis。用LJM11蛋白免疫的小鼠表现出抗lim11 IgG、IgG1和IgG2a的增加,以及以CD4(+) ifn - γ (+) T细胞存在的炎症浸润为特征的DTH反应。ljm11免疫小鼠在Lu存在的情况下耳部皮内感染巴西乳杆菌。长肌或陆肌。媒介物SGS。在巴西乳杆菌加Lu攻毒组中,耳朵和淋巴结的寄生虫数量显著减少。当巴西乳杆菌加Lu攻毒时,未观察到长掌肌SGS。媒介物SGS。感染后仅在LJM11免疫小鼠的淋巴结细胞中观察到更高的特异性ifn - γ的产生和IL-10的缺失。2周后,LJM11组和BSA组的CD4(+) ifn - γ (+) T细胞出现频率相似。这表明可能由免疫引起的早期事件对于预防利什曼原虫感染至关重要。我们的研究结果支持了唾液介导的免疫反应的特异性,并加强了识别交叉保护性唾液抗原的重要性。
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-LIM11 IgG, IgG1 and IgG2a and a DTH response characterized by an inflammatory infiltrate with the presence of CD4(+) IFN-gamma(+) 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-gamma 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-gamma(+) 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.