Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Mexico City , Mexico.
Facultad de Odontología, Universidad Nacional Autónoma de México , Mexico City , Mexico.
Front Immunol. 2014 May 27;5:236. doi: 10.3389/fimmu.2014.00236. eCollection 2014.
The PE_PGRS33 protein is a member of the PE family, which encompasses the PE and the PE_PGRS subfamilies. Among PE_PGRS's, this protein is one of the most studied antigens and its immunomodulatory properties are influence by both PE and PGRS domains. However, the contribution of these domains to the host immune recognition of the PE_PGRS33 protein and their potential role in latent tuberculosis infection in humans is still unknown. In this study, the immunogenic properties of the complete PE_PGRS33 protein and each domain separately were evaluated in BALB/c mice and latent tuberculosis infected (LTBI) humans. In mice, PE_PGRS33 and its domains induced similar antibody production and secretion of IFN-γ. PE_PGRS33 and the PE domain stimulated higher CD4(+) and CD8(+) T-cell proliferation compared to the PGRS domain. This demonstrated that the principal difference in the immune recognition of the domains is the higher activation of T-cell subpopulations involved in the control of tuberculosis. In humans, the secretion of IFN-γ in response to PE_PGRS33 was detected in both LTBI and in non-infected vaccinated individuals. The same was observed for antibody response, which targets epitopes located in the PGRS domain but not in the PE domain. These observations suggest that T and B cell responses to PE_PGRS33 are induced by BCG vaccination and can be maintained for many years in non-infected individuals. This also indicates that the IFN-γ response detected might not be associated with latent tuberculosis infection. These results contribute to the elucidation of the role of the PE_PGRS33 protein and its PE and PGRS domains in the immune response against Mycobacterium tuberculosis.
PE_PGRS33 蛋白是 PE 家族的成员，包括 PE 和 PE_PGRS 亚家族。在 PE_PGRS 中，该蛋白是研究最多的抗原之一，其免疫调节特性受 PE 和 PGRS 结构域的影响。然而，这些结构域对宿主对 PE_PGRS33 蛋白的免疫识别的贡献及其在人类潜伏性结核感染中的潜在作用尚不清楚。在这项研究中，我们在 BALB/c 小鼠和潜伏性结核感染（LTBI）人类中评估了完整的 PE_PGRS33 蛋白及其各个结构域的免疫原性。在小鼠中，PE_PGRS33 及其结构域诱导了相似的抗体产生和 IFN-γ 的分泌。与 PGRS 结构域相比，PE_PGRS33 和 PE 结构域刺激了更高的 CD4(+)和 CD8(+)T 细胞增殖。这表明，对结构域的免疫识别的主要区别在于涉及控制结核病的 T 细胞亚群的更高激活。在人类中，在 LTBI 和未感染的疫苗接种个体中均检测到针对 PE_PGRS33 的 IFN-γ 分泌。针对位于 PGRS 结构域而非 PE 结构域的表位的抗体反应也是如此。这些观察结果表明，针对 PE_PGRS33 的 T 和 B 细胞反应是由 BCG 疫苗接种诱导的，并可在未感染的个体中维持多年。这也表明，检测到的 IFN-γ 反应可能与潜伏性结核感染无关。这些结果有助于阐明 PE_PGRS33 蛋白及其 PE 和 PGRS 结构域在针对结核分枝杆菌的免疫反应中的作用。
