Prakash Sangeetha, Agrawal Sudhanshu, Ma Dandan, Gupta Sudhir, Peterson Ellena M, Agrawal Anshu
Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA.
Mediators Inflamm. 2014;2014:436438. doi: 10.1155/2014/436438. Epub 2014 Sep 1.
Chlamydophila pneumoniae (CPn) is a common respiratory pathogen that causes a chronic and persistent airway infection. The elderly display an increased susceptibility and severity to this infection. However, the underlying mechanisms are not well understood. Dendritic cells (DCs) are the initiators and regulators of immune responses. Therefore, we investigated the role of DCs in the age-associated increased CPn infection in vitro in humans. Though the expression of activation markers was comparable between the two age groups, DCs from aged subjects secreted enhanced levels of proinflammatory mediators such as TNF-α and CXCL-10 in response to CPn. In contrast, the secretion of IL-10 and innate interferons, IFN-α and IFN-λ, was severely impaired in DCs from aged donors. The increased activation of DCs from aged subjects to CPn also resulted in enhanced proliferation of CD4 and CD8 T cells in a DC-T coculture. Furthermore, T cells primed with CPn-stimulated DCs from aged subjects secreted increased levels of IFN-γ and reduced levels of IL-10 compared to DCs obtained from young subjects. In summary, DCs from the elderly displayed enhanced inflammatory response to CPn which may result in airway remodeling and increase the susceptibility of the elderly to respiratory diseases such as asthma.
肺炎衣原体（CPn）是一种常见的呼吸道病原体，可引起慢性持续性气道感染。老年人对此类感染的易感性和感染严重程度更高。然而，其潜在机制尚未完全明确。树突状细胞（DCs）是免疫反应的启动者和调节者。因此，我们在体外研究了人类DCs在年龄相关的CPn感染增加中所起的作用。尽管两个年龄组之间激活标志物的表达相当，但老年受试者的DCs在受到CPn刺激后分泌的促炎介质如TNF-α和CXCL-10水平更高。相反，老年供体的DCs中IL-10以及固有干扰素IFN-α和IFN-λ的分泌严重受损。老年受试者的DCs对CPn激活增加还导致DC-T共培养中CD4和CD8 T细胞增殖增强。此外，与年轻受试者来源的DCs相比，用老年受试者CPn刺激的DCs激活的T细胞分泌的IFN-γ水平增加，IL-10水平降低。总之，老年人的DCs对CPn表现出更强的炎症反应，这可能导致气道重塑，并增加老年人对哮喘等呼吸道疾病的易感性。
