Mackenzie-Dyck Sarah, Attah-Poku Sam, Juillard Veronique, Babiuk Lorne A, van Drunen Littel-van den Hurk Sylvia
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada.
Vet Immunol Immunopathol. 2011 Sep 15;143(1-2):87-107. doi: 10.1016/j.vetimm.2011.06.028. Epub 2011 Jun 24.
Human and murine immature DCs (iDCs) are highly efficient in antigen capture and processing, while as mature cells they present antigen and are potent initiators of cell-mediated immune responses. Consequently, iDCs are logical targets for vaccine antigens. Originally discovered for their antimicrobial activity, and thought of as strictly part of the innate immune system, studies with defensins such as human β (beta)-defensin 2 (hBD2) and murine β-defensin 2 (mBD2) have shown that they can function as chemo-attractant for iDCs and, in vaccination strategies, can enhance antigen-specific adaptive immune responses. Most studies to date have been conducted in mice. In contrast, little is known about defensins in cattle. To expand our understanding of the role of defensins in modulating immune responses in cattle, DCs were generated from bovine monocytes and the immature state of these bovine DCs was characterized phenotypically and through functional assays. By day 3 (DC3), bovine monocyte-derived DCs stained positively for DC-specific receptors CD1, CD80/86, CD205, DC-Lamp and MMR. When compared to conventional 6-day DC cultures or DCs cultured for 10 days with and without maturation factors, these DC3 were functionally at their most immature stage. Fourteen of the 16 known bovine β-defensins were synthesized and the synthetic peptides were screened for their ability to attract bovine iDCs. Bovine DC3 were consistently attracted to BNBD3, an analog of BNBD3 (aBNBD3), BNBD9 and bovine EBD in vitro and to aBNBD3 in vivo. These results are the first to describe chemotactic ability of synthetic bovine β-defensins for immature bovine monocyte-derived DCs.
人和小鼠的未成熟树突状细胞（iDCs）在抗原捕获和加工方面效率很高，而作为成熟细胞，它们呈递抗原，是细胞介导的免疫反应的有效启动者。因此，iDCs是疫苗抗原的合理靶点。防御素最初因其抗菌活性而被发现，并被认为是固有免疫系统的严格组成部分，对诸如人β（β）-防御素2（hBD2）和小鼠β-防御素2（mBD2）等防御素的研究表明，它们可以作为iDCs的趋化因子，并且在疫苗接种策略中，可以增强抗原特异性适应性免疫反应。迄今为止，大多数研究是在小鼠中进行的。相比之下，关于牛体内防御素的了解甚少。为了扩大我们对防御素在调节牛免疫反应中作用的理解，从牛单核细胞中生成了树突状细胞，并通过表型和功能测定对这些牛树突状细胞的未成熟状态进行了表征。到第3天（DC3）时，牛单核细胞衍生的树突状细胞对树突状细胞特异性受体CD1、CD80/86、CD205、DC-Lamp和MMR呈阳性染色。与传统的6天树突状细胞培养物或在有或没有成熟因子的情况下培养10天的树突状细胞相比，这些DC3在功能上处于最不成熟阶段。合成了16种已知牛β-防御素中的14种，并筛选了合成肽吸引牛iDCs的能力。牛DC3在体外始终被BNBD3、BNBD3的类似物（aBNBD3）、BNBD9和牛EBD吸引，在体内被aBNBD3吸引。这些结果首次描述了合成牛β-防御素对未成熟牛单核细胞衍生树突状细胞的趋化能力。
