The impact of cell maturation and tissue microenvironments on the expression of endosomal Toll-like receptors in monocytes and macrophages
The impact of cell maturation and tissue microenvironments on the expression of endosomal Toll-like receptors in monocytes and macrophages
复制标题
细胞成熟和组织微环境对单核细胞和巨噬细胞内体Toll样受体表达的影响
DOI：
10.1093/intimm/dxaa055
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发表时间：
2020
期刊：
影响因子：
4.4
通讯作者：
Miyake K.
中科院分区：
文献类型：
--
作者：
Sato R;Reuter T;Hiranuma R;Shibata T;Fukui R;Motoi Y;Murakami Y;Tsukamoto H;Yamazaki S;Liu K;Saitoh SI;Latz E;Miyake K.
Toll样受体（TLR）影响骨髓细胞对环境因素（如病原体组分和代谢物）的反应。尽管TLR蛋白在单核细胞和组织巨噬细胞中的表达被认为是针对每个组织中的微环境而优化的，但尚未报道全面的研究。我们在此检测了组织驻留髓样细胞中内源性TLR的蛋白表达。外周血、脾、肝和肺中的中性粒细胞在所有组织中表达TLR2、TLR4和TLR5。Ly6C+MHC II+经典单核细胞成熟为Ly6C + MHC II+单核细胞衍生的树突状细胞（moDCs）或Ly6C + MHC II+巡逻单核细胞。这些子集被发现在所有的组织研究。TLR2和TLR4在所有这些亚群上均显示，无论位置如何。相反，内体TLR的表达确实随组织和亚群而变化。moDC表达TLR9，但TLR7表达较少。相反，TLR7，而不是TLR3或TLR9，在经典和巡逻单核细胞中高度表达。组织巨噬细胞如脾中的红髓巨噬细胞、肝中的枯否细胞、脑中的小胶质细胞、肺中的肺泡巨噬细胞和脂肪组织巨噬细胞均表达TLR 2、TLR 4和TLR 3。TLR7也在这些组织中的巨噬细胞中表达，但肝脏中的枯否细胞除外。TLR9在组织巨噬细胞中的表达低得多或难以检测。这些结果表明，髓样细胞中的内体TLR的表达受到其分化状态和组织特异性微环境的影响。
Toll-like receptors (TLRs) impact myeloid cell responsiveness to environmental cues such as pathogen components and metabolites. Although TLR protein expression in monocytes and tissue macrophages is thought to be optimized for microenvironments in each tissue, a comprehensive study has not been reported. We here examined protein expression of endogenous TLRs in tissue-resident myeloid cells. Neutrophils in peripheral blood, spleen, liver and lung expressed TLR2, TLR4 and TLR5 in all tissues. Ly6C+MHC II‒classical monocytes mature into Ly6C‒MHC II+monocyte-derived dendritic cells (moDCs) or Ly6C‒MHC II‒patrolling monocytes. These subsets were found in all the tissues studied. TLR2 and TLR4 were displayed on all of these subsets, regardless of location. In contrast, expression of endosomal TLRs did vary with tissues and subsets. moDCs expressed TLR9, but much less TLR7. In contrast, TLR7, not TLR3 or TLR9, was highly expressed in classical and patrolling monocytes. Tissue macrophages such as red pulp macrophages in the spleen, Kupffer cells in the liver, microglia in the brain, alveolar macrophages in the lung and adipose tissue macrophages all expressed TLR2, TLR4 and TLR3. TLR7 was also expressed in these tissue macrophages except Kupffer cells in the liver. TLR9 expression in tissue macrophages was much lower or hard to detect. These results suggest that expression of endosomal TLRs in myeloid cells is influenced by their differentiation status and tissue-specific microenvironments.