Awasthi Shanjana, Awasthi Vibhudutta, Magee D Mitchell, Coalson Jacqueline J
Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
J Immunol. 2005 Sep 15;175(6):3900-6. doi: 10.4049/jimmunol.175.6.3900.
Coccidioides posadasii causes coccidioidomycosis, or Valley fever, in the endemic regions of the Southwestern United States. The susceptibility to C. posadasii infection has been attributed to a decreased Th1 cellular response. APCs, especially dendritic cells (DCs), play an important role in the activation of Th1 response. In this study, we investigated the efficacy of a DC-based vaccine against C. posadasii in a mouse model of coccidioidomycosis. We intranasally immunized C57BL6 mice with syngeneic, bone marrow-derived DCs (JAWS II cells) transfected with a cDNA encoding the protective Coccidioides-Ag2/proline-rich Ag. The immunized mice were lethally challenged with C. posadasii through either an i.p. or intranasal route. Upon necropsy after 10 days of infection, fungal burden in lung and spleen of immunized mice was significantly reduced as compared with the control animals. The lung tissue homogenates of immunized animals showed higher levels of IFN-gamma. Histologically, lung tissues of immunized mice were in better condition than the control mice. To further investigate, we studied the biodistribution and trafficking of injected DCs by nuclear imaging techniques. For this purpose, the transfected DCs were radiolabeled with (111)In-oxime. Scintigraphic images showed that most of the label remained in the gastrointestinal tract. A significant amount was also observed in lung, but there were negligible circulating (111)In label in blood. The results suggest that the DCs have a potent immunostimulatory activity, and immunization with DCs transfected with Ag2/proline-rich Ag-cDNA induces protective immunity against C. posadasii in C57BL6 mice.
波萨达斯球孢子菌在美国西南部的流行地区可引发球孢子菌病，即山谷热。对波萨达斯球孢子菌感染的易感性归因于Th1细胞反应减弱。抗原呈递细胞（APCs），尤其是树突状细胞（DCs），在Th1反应的激活中起重要作用。在本研究中，我们在球孢子菌病小鼠模型中研究了一种基于树突状细胞的疫苗对波萨达斯球孢子菌的疗效。我们用编码保护性球孢子菌-Ag2/富含脯氨酸抗原的cDNA转染的同基因骨髓来源树突状细胞（JAWS II细胞）经鼻免疫C57BL6小鼠。免疫后的小鼠通过腹腔注射或经鼻途径接受波萨达斯球孢子菌的致死性攻击。感染10天后尸检发现，与对照动物相比，免疫小鼠肺和脾中的真菌负荷显著降低。免疫动物的肺组织匀浆显示出更高水平的干扰素-γ。组织学检查显示，免疫小鼠的肺组织状况优于对照小鼠。为了进一步研究，我们通过核成像技术研究了注射的树突状细胞的生物分布和转运情况。为此，将转染的树突状细胞用（111）In-肟进行放射性标记。闪烁图像显示，大部分标记物仍留在胃肠道。在肺中也观察到大量标记物，但血液中循环的（111）In标记物可忽略不计。结果表明，树突状细胞具有强大的免疫刺激活性，用Ag2/富含脯氨酸抗原-cDNA转染的树突状细胞免疫可诱导C57BL6小鼠对波萨达斯球孢子菌产生保护性免疫。
