Abstract

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.

中文翻译：

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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。

摘要

Toll 样受体 (TLR) 会影响髓细胞对病原体成分​​和代谢物等环境因素的反应。尽管单核细胞和组织巨噬细胞中的 TLR 蛋白表达被认为是针对每个组织中的微环境进行了优化，但尚未报道过全面的研究。我们在这里检查了组织驻留骨髓细胞中内源性 TLR 的蛋白质表达。外周血、脾脏、肝脏和肺中的中性粒细胞在所有组织中均表达 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细胞 (moDC) 或 Ly6C ^‒ MHC II ^‒巡逻单核细胞。在所有研究的组织中都发现了这些亚群。无论位置如何，TLR2 和 TLR4 都显示在所有这些子集上。相比之下，内体 TLR 的表达确实因组织和亚群而异。moDCs 表达 TLR9，但较少表达 TLR7。相比之下，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、肝脏中的库普弗细胞、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 TLR2、TLR4 和 TLR3。除了肝脏中的库普弗细胞外，TLR7 也在这些组织巨噬细胞中表达。组织巨噬细胞中的 TLR9 表达要低得多或难以检测。