Departamento de Bioquímica Clínica-Facultad de Ciencias Químicas, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI, CONICET-UNC), Universidad Nacional de Córdoba, Córdoba, Argentina.
Centro de Investigation en Medicina Traslacional Severo Amuchastegui - (CIMETSA) - Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.
Immunology. 2022 Sep;167(1):64-76. doi: 10.1111/imm.13518. Epub 2022 Jun 25.
In the gut, secretory immunoglobulin A is the predominant humoral response against commensals, although healthy hosts also produce microbiota-specific IgG antibodies. During intestinal inflammation, the content of IgG in the lumen increases along with the proportion of commensal bacteria coated with this antibody, suggesting signalling through the IgG-CD64 axis in the pathogenesis of inflammatory bowel diseases. In this work, we evaluated day by day the frequency of faecal bacteria coated with IgA and IgG during the development of DSS colitis. We studied the phenotype and phagocytic activity of F4/80 CD64 colonic macrophages, as well as the production of cytokines and nitric oxide by lamina propria or bone marrow-derived macrophages after stimulation with IgA , IgG and IgA IgG bacteria. We found that the percentage of faecal IgA IgG double-coated bacteria increased rapidly during DSS colitis. Also, analysis of the luminal content of mice with colitis showed a markedly superior ability to coat fresh bacteria. IgA IgG bacteria were the most potent stimulus for phagocytic activity involving CD64 and Dectin-1 receptors. IgA IgG bacteria observed during the development of DSS colitis could represent a new marker to monitor permeability and inflammatory progression. The interaction of IgA IgG bacteria with CD64 F4/80 macrophages could be part of the complex cascade of events in colitis. Interestingly, after stimulation, CD64 colonic macrophages showed features similar to those of restorative macrophages that are relevant for tissue repair and healing.
在肠道中，分泌型免疫球蛋白 A 是针对共生菌的主要体液免疫反应，尽管健康宿主也会产生针对微生物组特异性的 IgG 抗体。在肠道炎症期间，腔内容物中 IgG 的含量会增加，同时伴有被这种抗体包裹的共生菌比例增加，这表明 IgG-CD64 轴在炎症性肠病的发病机制中发挥作用。在这项工作中，我们在 DSS 结肠炎的发展过程中每天评估粪便中被 IgA 和 IgG 包裹的细菌的频率。我们研究了 F4/80 CD64 结肠巨噬细胞的表型和吞噬活性，以及用 IgA、IgG 和 IgA IgG 细菌刺激后，固有层或骨髓来源的巨噬细胞产生细胞因子和一氧化氮的情况。我们发现，在 DSS 结肠炎期间，粪便中 IgA IgG 双包裹细菌的比例迅速增加。此外，对结肠炎小鼠腔内容物的分析表明，其对新鲜细菌的包裹能力明显更强。IgA IgG 细菌是涉及 CD64 和 Dectin-1 受体的吞噬活性的最有效刺激物。在 DSS 结肠炎发展过程中观察到的 IgA IgG 细菌可能是监测通透性和炎症进展的一个新标志物。IgA IgG 细菌与 CD64 F4/80 巨噬细胞的相互作用可能是结肠炎中复杂级联事件的一部分。有趣的是，刺激后，CD64 结肠巨噬细胞表现出与参与组织修复和愈合的修复性巨噬细胞相似的特征。
