Ontiveros-Padilla Luis, García-Lozano Alberto, Tepale-Segura Araceli, Rivera-Hernández Tania, Pastelin-Palacios Rodolfo, Isibasi Armando, Arriaga-Pizano Lourdes A, Bonifaz Laura C, López-Macías Constantino
Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Cuauhtemoc, Ciudad de Mexico 06720, Mexico.
Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Coyoacan, Ciudad de Mexico 04510, Mexico.
Microorganisms. 2021 Apr 7;9(4):770. doi: 10.3390/microorganisms9040770.
serovar Typhi (. Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against . Typhi in mice and humans. Vaccination with porins induces the protection against 500 LD of . Typhi, life-lasting bactericidal antibodies and effector T cell responses in mice; however, the nature of the memory T cell compartment and its contribution to protection remains unknown. In this work, we firstly observed that vaccination with porins induces in situ (skin) CD4+ and CD8+ T cell responses. Analysis of the porin-specific functional responses of skin CD4+ and CD8+ T cells showed IFN-gamma- and IL-17-producing cells in both T cell populations. The memory phenotype of porin-specific T cells indicated the presence of resident and effector memory phenotypes in the skin, and a central memory phenotype in the skin-draining lymph node. In addition, we demonstrated that vaccination with porins via skin reduces the bacterial burden following challenge. Finally, evaluating the role of the circulating T cell memory population in protection, we showed that circulating memory CD4+ and CD8+ T cells are crucial in porin-mediated protection against . Typhi. Overall, this study highlights the importance of inducing circulating memory T cell responses in order to achieve the optimal protection provided by porins, showing a mechanism that could be sought in the rational development of vaccines.
伤寒血清型（伤寒杆菌）的孔蛋白OmpC和OmpF是小鼠和人类中针对伤寒杆菌免疫反应的有效诱导剂。用孔蛋白进行疫苗接种可诱导小鼠抵抗500个致死剂量的伤寒杆菌，产生持久的杀菌抗体和效应T细胞反应；然而，记忆T细胞区室的性质及其对保护作用的贡献仍然未知。在这项研究中，我们首先观察到用孔蛋白进行疫苗接种可诱导原位（皮肤）CD4+和CD8+ T细胞反应。对皮肤CD4+和CD8+ T细胞的孔蛋白特异性功能反应分析显示，两个T细胞群体中均有产生IFN-γ和IL-17的细胞。孔蛋白特异性T细胞的记忆表型表明皮肤中存在驻留记忆和效应记忆表型，以及皮肤引流淋巴结中的中枢记忆表型。此外，我们证明通过皮肤用孔蛋白进行疫苗接种可在攻击后减轻细菌负荷。最后，评估循环T细胞记忆群体在保护中的作用，我们发现循环记忆CD4+和CD8+ T细胞在孔蛋白介导的抵抗伤寒杆菌的保护中至关重要。总体而言，这项研究强调了诱导循环记忆T细胞反应对于实现孔蛋白提供的最佳保护的重要性，展示了一种在疫苗合理开发中可探寻的机制。
