Department Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands.
Mol Immunol. 2013 Dec;56(4):452-62. doi: 10.1016/j.molimm.2013.06.007. Epub 2013 Aug 1.
To increase our understanding of the interaction between avian influenza virus and its chicken host, we identified receptors for putative avian influenza virus (AIV) glycan determinants on chicken dendritic cells. Chicken dendritic cells (DCs) were found to recognize glycan determinants containing terminal αGalNAc, Galα1-3Gal, GlcNAcβ1-4GlcNAcβ1-4GlcNAcβ (chitotriose) and Galα1-2Gal. Infection of chicken dendritic cells with either low pathogenic (LP) or highly pathogenic (HP) AIV results in elevated mRNA expression of homologs of the mouse C-type lectins DEC205 and macrophage mannose receptor (MMR), whereas expression levels of the human dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) homolog remained unchanged. Following uptake and subsequent presentation of avian influenza virus by DCs, adaptive immunity, including humoral immune responses are induced. We have investigated the antibody responses against virus glycan epitopes after avian influenza virus infection. Using glycan micro-array analysis we showed that chicken contained antibodies that predominantly recognize terminal Galα1-3Gal-R, chitotriose and Fucα1-2Galβ1-4GlcNAc-R (H-type 2). After influenza-infection, glycan array analysis showed that both levels and repertoire of glycan-recognizing antibodies decreased. However, analysis of the sera by ELISA indicated that the levels of different isotypes of anti-glycan Abs against specific glycan antigens was increased after influenza-infection, suggesting that the presentation of the glycan antigens and iso-type of the Abs are critical parameters to take into account when measuring anti-glycan Abs. This novel approach in avian influenza research may contribute to the development of a broad spectrum vaccine and improves our mechanistic understanding of innate and adaptive responses to glycans.
为了增进我们对禽流感病毒与其鸡宿主相互作用的了解，我们鉴定了鸡树突状细胞上可能的禽流感病毒糖决定簇的受体。鸡树突状细胞（DC）被发现可识别含有末端αGalNAc、Galα1-3Gal、GlcNAcβ1-4GlcNAcβ1-4GlcNAcβ（壳三糖）和Galα1-2Gal 的糖决定簇。低致病性（LP）或高致病性（HP）禽流感病毒感染鸡树突状细胞后，鼠 C 型凝集素 DEC205 和巨噬细胞甘露糖受体（MMR）的同源物的 mRNA 表达水平升高，而人树突状细胞特异性细胞间黏附分子-3 抓取非整合素（DC-SIGN）同源物的表达水平保持不变。树突状细胞摄取和随后呈递禽流感病毒后，会诱导适应性免疫，包括体液免疫反应。我们研究了禽流感病毒感染后针对病毒糖决定簇的抗体反应。通过糖微阵列分析，我们发现鸡体内含有主要识别末端 Galα1-3Gal-R、壳三糖和 Fucα1-2Galβ1-4GlcNAc-R（H 型 2）的抗体。流感感染后，糖微阵列分析显示糖识别抗体的水平和 repertoire 均降低。然而，通过 ELISA 分析血清表明，针对特定糖抗原的不同糖结合抗体同种型的水平在流感感染后增加，这表明糖抗原的呈递和同种型的 Abs 是测量糖结合 Abs 时需要考虑的关键参数。这种在禽流感研究中的新方法可能有助于广谱疫苗的开发，并提高我们对糖基先天和适应性反应的机制理解。
