Ngantcha Tatchou Elie, Milcamps Romane, Oldenhove Guillaume, Lambrecht Bénédicte, Ingrao Fiona
Service of Avian Virology and Immunology, Sciensano, Brussels, Belgium.
Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
Front Immunol. 2025 Feb 4;16:1517697. doi: 10.3389/fimmu.2025.1517697. eCollection 2025.
Dendritic cells (DCs) play a crucial role in orchestrating immune responses by bridging innate and adaptive immunity. generation of DCs from mouse and human tissues such as bone marrow and peripheral blood monocytes, has been widely used to study their immunological functions. In chicken, DCs have mainly been derived from bone marrow cell cultures, with limited characterization from blood monocytes.
The present study takes advantage of newly available chicken immunological tools to further characterize chicken monocyte-derived dendritic cells (MoDCs), focusing on their phenotype, and functions, including antigen capture and T-cell stimulation, and response to live Newcastle disease virus (NDV) stimulation.
Adherent chicken PBMCs were cultured with recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), for 5 days, leading to the upregulation of putative CD11c and MHCII, markers of DC differentiation. Subsequent stimulation with lipopolysaccharide (LPS) or 24 h triggered phenotypic maturation of MoDCs, characterized by the increased surface expression of MHCII and co-stimulatory molecules CD80 and CD40, and elevated IL-12p40 secretion. This maturation reduced endocytic capacity but enhanced the allogenic stimulatory activity of the chicken MoDCs. Upon NDV stimulation for 6 h, MoDCs upregulated antiviral pathways, including retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), melanoma differentiation-associated protein 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2), alongside increased production of type I interferons (IFNs), and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-1β, and IL-6. However, these responses were downregulated after 24 hours.
These findings provide a comprehensive characterization of chicken MoDCs and suggest their potential as a model for studying host-pathogen interactions.
树突状细胞（DCs）通过连接天然免疫和适应性免疫在协调免疫反应中发挥关键作用。从小鼠和人类组织（如骨髓和外周血单核细胞）中生成DCs已被广泛用于研究其免疫功能。在鸡中，DCs主要来源于骨髓细胞培养物，而对血液单核细胞的特征描述有限。
本研究利用新获得的鸡免疫工具进一步表征鸡单核细胞衍生的树突状细胞（MoDCs），重点关注其表型、功能，包括抗原捕获和T细胞刺激，以及对活新城疫病毒（NDV）刺激的反应。
贴壁的鸡外周血单核细胞与重组鸡粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）一起培养5天，导致假定的DC分化标志物CD11c和MHCII上调。随后用脂多糖（LPS）刺激或24小时触发MoDCs的表型成熟，其特征是MHCII和共刺激分子CD80和CD40的表面表达增加，以及IL-12p40分泌升高。这种成熟降低了内吞能力，但增强了鸡MoDCs的同种异体刺激活性。在NDV刺激6小时后，MoDCs上调抗病毒途径，包括视黄酸诱导基因I（RIG-I）样受体（RLRs）、黑色素瘤分化相关蛋白5（MDA5）和遗传学与生理学实验室2（LGP2），同时I型干扰素（IFNs）以及促炎细胞因子肿瘤坏死因子-α（TNF-α）、IL-1β和IL-6的产生增加。然而，这些反应在24小时后下调。
这些发现全面表征了鸡MoDCs，并表明它们作为研究宿主-病原体相互作用模型的潜力。
