GRI, Groupe de recherche en immunopathologie, EA4517, Université de la Réunion, Saint-Denis, France.
Université de La Réunion, INSERM 1188, Diabète athérothombose Réunion Océan Indien (DéTROI), Saint-Denis de La Réunion, France.
Immunology. 2019 Oct;158(2):85-93. doi: 10.1111/imm.13100. Epub 2019 Jul 23.
Bacterial DNA contains CpG oligonucleotide (ODN) motifs to trigger innate immune responses through the endosomal receptor Toll-like receptor 9 (TLR9). One of the cell surface receptors to capture and deliver microbial DNA to intracellular TLR9 is the C-type lectin molecule DEC-205 through its N-terminal C-type lectin-like domain (CTLD). CD93 is a cell surface protein and member of the lectin group XIV with a CTLD. We hypothesized that CD93 could interact with CpG motifs, and possibly serve as a novel receptor to deliver bacterial DNA to endosomal TLR9. Using ELISA and tryptophan fluorescence binding studies we observed that the soluble histidine-tagged CD93-CTLD was specifically binding to CpG ODN and bacterial DNA. Moreover, we found that CpG ODN could bind to CD93-expressing IMR32 neuroblastoma cells and induced more robust interleukin-6 secretion when compared with mock-transfected IMR32 control cells. Our data argue for a possible contribution of CD93 to control cell responsiveness to bacterial DNA in a manner reminiscent of DEC-205. We postulate that CD93 may act as a receptor at plasma membrane for DNA or CpG ODN and to grant delivery to endosomal TLR9.
细菌 DNA 含有 CpG 寡核苷酸 (ODN) 基序，通过内体受体 Toll 样受体 9 (TLR9) 触发先天免疫反应。捕获并将微生物 DNA 递送至细胞内 TLR9 的细胞表面受体之一是 C 型凝集素分子 DEC-205，通过其 N 端 C 型凝集素样结构域 (CTLD)。CD93 是一种细胞表面蛋白，是具有 CTLD 的凝集素组 XIV 的成员。我们假设 CD93 可以与 CpG 基序相互作用，并可能作为一种新型受体将细菌 DNA 递送至内体 TLR9。通过 ELISA 和色氨酸荧光结合研究，我们观察到可溶性组氨酸标记的 CD93-CTLD 特异性结合 CpG ODN 和细菌 DNA。此外，我们发现 CpG ODN 可以结合表达 CD93 的 IMR32 神经母细胞瘤细胞，并与模拟转染的 IMR32 对照细胞相比，诱导更强的白细胞介素-6 分泌。我们的数据表明，CD93 可能以类似于 DEC-205 的方式对控制细胞对细菌 DNA 的反应性做出贡献。我们假设 CD93 可能作为质膜上的受体，用于 DNA 或 CpG ODN，并将其递送至内体 TLR9。
