Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Medina Allende y Haya de la Torre, Ciudad Universitaria, Córdoba, Argentina.
Immunology. 2011 Oct;134(2):198-213. doi: 10.1111/j.1365-2567.2011.03479.x.
Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, because as in healthy humans, rats can effectively contain cryptococcal infection. Moreover, it has been shown that eosinophils are components of the immune response to C. neoformans infections. In a previous in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, thereby triggering their activation, as indicated by the up-regulation of MHC and co-stimulatory molecules and the increase in interleukin-12, tumour necrosis factor-α and interferon-γ production. Furthermore, this work demonstrated that C. neoformans-specific CD4(+) and CD8(+) T lymphocytes cultured with these activated C. neoformans-pulsed eosinophils proliferated, and produced important amounts of T helper type 1 (Th1) cytokines in the absence of Th2 cytokine synthesis. In the present in vivo study, we have shown that C. neoformans-pulsed eosinophils are also able to migrate into lymphoid organs to present C. neoformans antigens, thereby priming naive and re-stimulating infected rats to induce T-cell and B-cell responses against infection with the fungus. Furthermore, the antigen-specific immune response induced by C. neoformans-pulsed eosinophils, which is characterized by the development of a Th1 microenvironment with increased levels of NO synthesis and C. neoformans-specific immunoglobulin production, was demonstrated to be able to protect rats against subsequent infection with fungus. In summary, the present work demonstrates that eosinophils act as antigen-presenting cells for the fungal antigen, hence initiating and modulating a C. neoformans-specific immune response. Finally, we suggest that C. neoformans-loaded eosinophils might participate in the protective immune response against these fungi.
实验性新生隐球菌感染大鼠与人类隐球菌病具有相似性，因为与健康人类一样，大鼠可以有效地控制隐球菌感染。此外，研究表明嗜酸性粒细胞是针对新生隐球菌感染的免疫反应的组成部分。在之前的一项体外研究中，我们证明了大鼠腹腔嗜酸性粒细胞吞噬调理后的活新生隐球菌酵母，从而触发其激活，表现为 MHC 和共刺激分子的上调以及白细胞介素-12、肿瘤坏死因子-α和干扰素-γ的产生增加。此外，这项工作表明，与这些激活的新生隐球菌-脉冲嗜酸性粒细胞共培养的新生隐球菌特异性 CD4+和 CD8+T 淋巴细胞增殖，并在没有 Th2 细胞因子合成的情况下产生大量 Th1 型（Th1）细胞因子。在本体内研究中，我们已经表明，新生隐球菌-脉冲嗜酸性粒细胞也能够迁移到淋巴器官呈递新生隐球菌抗原，从而启动幼稚和重新刺激感染大鼠，以诱导针对真菌感染的 T 细胞和 B 细胞反应。此外，由新生隐球菌-脉冲嗜酸性粒细胞诱导的抗原特异性免疫反应，其特征是产生增加的 NO 合成和新生隐球菌特异性免疫球蛋白产生的 Th1 微环境，被证明能够保护大鼠免受后续真菌感染。总之，本工作表明，嗜酸性粒细胞作为真菌抗原的呈递细胞，从而启动并调节针对新生隐球菌的免疫反应。最后，我们建议新生隐球菌负载的嗜酸性粒细胞可能参与针对这些真菌的保护性免疫反应。
