García-Lozano Alberto, Toriello Conchita, Antonio-Herrera Laura, Bonifaz Laura C
Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Microbiol. 2018 Jun 12;9:1275. doi: 10.3389/fmicb.2018.01275. eCollection 2018.
Sporotrichosis is a chronic subcutaneous mycosis caused by the species complex and it is considered an emerging opportunistic infection in countries with tropical and subtropical climates. The host's immune response has a main role in the development of this disease. However, it is unknown the features of the memory cellular immune response that could protect against the infection. Our results show that i.d. immunization in the ears of mice with inactivated conidia (iC) combined with the cholera toxin (CT) induces a cellular immune response mediated by circulating memory CD4 T cells, which mainly produce interleukin 17 (IL-17). These cells mediate a strong delayed-type hypersensitivity (DTH) reaction. Systemic and local protection against was mediated by circulating CD4 T cells. In contrast, the infection induces a potent immune response in the skin mediated by CD4 T cells, which have an effector phenotype that preferentially produce interferon gamma (IFN-γ) and mediate a transitory DTH reaction. Our findings prove the potential value of the CT as a potent skin adjuvant when combined with fungal antigens, and they also have important implications for our better understanding of the differences between the memory immune response induced by the skin immunization and those induced by the infection; this knowledge enhances our understanding of how a protective immune response against a infection is developed.
孢子丝菌病是由该菌种复合体引起的一种慢性皮下真菌病,在热带和亚热带气候国家被视为一种新兴的机会性感染。宿主的免疫反应在这种疾病的发展中起主要作用。然而,能够预防感染的记忆性细胞免疫反应的特征尚不清楚。我们的结果表明,在小鼠耳部皮内免疫灭活分生孢子(iC)并联合霍乱毒素(CT)可诱导由循环记忆性CD4 T细胞介导的细胞免疫反应,这些细胞主要产生白细胞介素17(IL-17)。这些细胞介导强烈的迟发型超敏反应(DTH)。针对申克孢子丝菌的全身和局部保护由循环CD4 T细胞介导。相比之下,感染在皮肤中诱导由CD4 T细胞介导的强效免疫反应,这些细胞具有优先产生干扰素γ(IFN-γ)并介导短暂DTH反应的效应表型。我们的研究结果证明了CT与真菌抗原联合时作为强效皮肤佐剂的潜在价值,并且它们对于我们更好地理解皮肤免疫诱导的记忆免疫反应与感染诱导的记忆免疫反应之间的差异也具有重要意义;这一知识增强了我们对如何产生针对申克孢子丝菌感染的保护性免疫反应的理解。