Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil; Departamento de Parasitologia e Microbiologia, Centro de Ciências da Saúde, Universidade Federal do Piauí, Teresina, Piauí, Brazil.
Centro de Ciências Agrárias, Universidade Federal do Piauí, Teresina, Piauí, Brazil.
PLoS Negl Trop Dis. 2014 Mar 13;8(3):e2729. doi: 10.1371/journal.pntd.0002729. eCollection 2014 Mar.
A recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi (rLdccys1) was previously shown to induce protective immune responses against murine and canine visceral leishmaniasis. These findings encouraged us to use rLdccys1 in the immunotherapy of naturally infected dogs from Teresina, Piauí, a region of high incidence of visceral leishmaniasis in Brazil.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty naturally infected mongrel dogs displaying clinical signs of visceral leishmaniasis were randomly divided in three groups: one group received three doses of rLdccys1 in combination with the adjuvant Propionibacterium acnes at one month interval between each dose; a second group received three doses of P. acnes alone; a third group received saline. The main findings were: 1) dogs that received rLdccys1 with P. acnes did not display increase of the following clinical signs: weight loss, alopecia, onychogryphosis, cachexia, anorexia, apathy, skin lesions, hyperkeratosis, ocular secretion, and enlarged lymph nodes; they also exhibited a significant reduction in the spleen parasite load in comparison to the control dogs; 2) rLdccys1-treated dogs exhibited a significant delayed type cutaneous hypersensitivity elicited by the recombinant antigen, as well as high IgG2 serum titers and low IgG1 serum titers; sera from rLdccys1-treated dogs also contained high IFN-γ and low IL-10 concentrations; 3) control dogs exhibited all of the clinical signs of visceral leishmaniasis and had low serum IgG2 and IFN-γ levels and high concentrations of IgG1 and IL-10; 4) all of the dogs treated with rLdccys1 were alive 12 months after treatment, whereas dogs which received either saline or P. acnes alone died within 3 to 7 months.
CONCLUSIONS/SIGNIFICANCE: These findings illustrate the potential use of rLdccys1 as an additional tool for the immunotherapy of canine visceral leishmaniasis and support further studies designed to improve the efficacy of this recombinant antigen for the treatment of this neglected disease.
先前已证明，来自恰加斯利什曼原虫（Leishmania）婴儿亚种（rLdccys1）的重组半胱氨酸蛋白酶可诱导针对鼠和犬内脏利什曼病的保护性免疫应答。这些发现促使我们在巴西内脏利什曼病高发地区皮奥伊州特雷西纳的自然感染犬中使用 rLdccys1 进行免疫治疗。
方法/主要发现：30 只表现出内脏利什曼病临床症状的自然感染杂种犬被随机分为三组：一组接受 rLdccys1 三次剂量，每次剂量间隔一个月，并用丙酸杆菌（Propionibacterium acnes）作为佐剂；第二组单独接受三次丙酸杆菌剂量；第三组接受生理盐水。主要发现如下：1）接受 rLdccys1 和丙酸杆菌的犬未出现以下临床症状的增加：体重减轻、脱毛、爪甲变形、恶病质、厌食、冷漠、皮肤损伤、过度角化、眼部分泌物和淋巴结肿大；与对照组犬相比，它们的脾脏寄生虫负荷也显著降低；2）rLdccys1 治疗的犬对重组抗原表现出显著的迟发型皮肤超敏反应，以及高 IgG2 血清滴度和低 IgG1 血清滴度；rLdccys1 治疗犬的血清还含有高 IFN-γ 和低 IL-10 浓度；3）对照组犬出现所有内脏利什曼病的临床症状，且血清 IgG2 和 IFN-γ 水平较低，IgG1 和 IL-10 浓度较高；4）接受 rLdccys1 治疗的犬在治疗后 12 个月内全部存活，而接受生理盐水或单独丙酸杆菌治疗的犬在 3 至 7 个月内死亡。
结论/意义：这些发现表明 rLdccys1 可作为犬内脏利什曼病免疫治疗的附加工具，支持进一步研究以提高该重组抗原治疗这种被忽视疾病的疗效。
