Antigen Sampling CSF1R-Expressing Epithelial Cells Are the Functional Equivalents of Mammalian M Cells in the Avian Follicle-Associated Epithelium
Antigen Sampling CSF1R-Expressing Epithelial Cells Are the Functional Equivalents of Mammalian M Cells in the Avian Follicle-Associated Epithelium
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DOI：
10.3389/fimmu.2019.02495
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发表时间：
2019-10-22
影响因子：
7.3
通讯作者：
Vervelde, Lonneke
中科院分区：
文献类型：
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作者：
Balic, Adam;Chintoan-Uta, Cosmin;Vervelde, Lonneke
滤泡相关上皮（FAE）是一种特殊的结构，它采集腔内抗原并将其转运到粘膜相关淋巴组织（MALT）。在哺乳动物中，抗原跨肠上皮的胞吞作用是由FAE细胞的一个亚群即M细胞完成的。在这里，我们发现集落刺激因子1受体（CSF1R）在fabicius FAE的禽法氏囊的一个细胞亚群中表达。最初使用csf1r报告基因检测表达，该基因也标记法氏囊巨噬细胞亚群。特异性单克隆抗体免疫组化检测证实CSF1R在FAE细胞基底外侧膜上大量表达。表达法氏囊FAE细胞的csf1r转基因富集表达了先前报道的推定的M细胞标记物，包括膜联蛋白A10和CD44。通过高顶端F-actin表达和凝集素jacalin、PHA-L和SNA的差异染色，进一步将它们与FAE内的csf1r转基因阴性上皮细胞群区分开来。表达csf1r报告基因的法氏囊FAE细胞负责0.02-0.1 μ m标记微颗粒的大部分FAE胞吞。与哺乳动物m细胞不同，它们不容易吸收较大的细菌大小的微颗粒（0.5 μ m）。它们在细菌摄取中的作用是用沙门氏菌来测试的，沙门氏菌可以通过哺乳动物的M细胞进入。标记的肠炎沙门氏菌血清型鼠伤寒沙门氏菌通过FAE进入法氏囊组织。进入部分依赖于III型分泌系统-1。然而，大多数入侵细菌定位于csf1r阴性FAE细胞和表达磷脂酰丝氨酸受体TIM4的常驻吞噬细胞。感染卵泡中表达csf1r的FAE细胞显示细胞死亡并脱落到法氏囊腔。在哺乳动物中，CSF1R在肠道中的表达仅限于巨噬细胞，而巨噬细胞仅间接控制M细胞的分化。鸟类中CSF1R的新表达表明，这些与哺乳动物M细胞功能等同的细胞可能具有不同的本体起源，其发育和功能可能受到不同生长因子的调控。
The follicle-associated epithelium (FAE) is a specialized structure that samples luminal antigens and transports them into mucosa-associated lymphoid tissues (MALT). In mammals, transcytosis of antigens across the gut epithelium is performed by a subset of FAE cells known as M cells. Here we show that colony-stimulating factor 1 receptor (CSF1R) is expressed by a subset of cells in the avian bursa of Fabricius FAE. Expression was initially detected using a CSF1R-reporter transgene that also label subsets of bursal macrophages. Immunohistochemical detection using a specific monoclonal antibody confirmed abundant expression of CSF1R on the basolateral membrane of FAE cells. CSF1R-transgene expressing bursal FAE cells were enriched for expression of markers previously reported as putative M cell markers, including annexin A10 and CD44. They were further distinguished from a population of CSF1R-transgene negative epithelial cells within FAE by high apical F-actin expression and differential staining with the lectins jacalin, PHA-L and SNA. Bursal FAE cells that express the CSF1R-reporter transgene were responsible for the bulk of FAE transcytosis of labeled microparticles in the size range 0.02-0.1 mu m. Unlike mammalian M cells, they did not readily take up larger bacterial sized microparticles (0.5 mu m). Their role in uptake of bacteria was tested using Salmonella, which can enter via M cells in mammals. Labeled Salmonella enterica serovar Typhimurium entered bursal tissue via the FAE. Entry was partially dependent upon Type III secretion system-1. However, the majority of invading bacteria were localized to CSF1R-negative FAE cells and in resident phagocytes that express the phosphatidylserine receptor TIM4. CSF1R-expressing FAE cells in infected follicles showed evidence of cell death and shedding into the bursal lumen. In mammals, CSF1R expression in the gut is restricted to macrophages which only indirectly control M cell differentiation. The novel expression of CSF1R in birds suggests that these functional equivalents to mammalian M cells may have different ontological origins and their development and function are likely to be regulated by different growth factors.