Galectin-9 is a member of the galectin family of proteins, which were first identified to specifically bind to carbohydrates containing β-galactosides. Galectin-9 is conserved through evolution and recent evidence demonstrated its involvement in innate immune reactions to bacterial infections as well as the suppression of cytotoxic immune responses of T and natural killer cells. However, the molecular mechanisms underlying such differential immunological functions of galectin-9 remain largely unknown. In this work we confirmed that soluble galectin-9 derived from macrophages binds to Gram-negative bacteria by interacting with lipopolysaccharide (LPS), which forms their cell wall. This opsonisation effect most likely interferes with the mobility of bacteria leading to their phagocytosis by innate immune cells. Galectin-9-dependent opsonisation also promotes the innate immune reactions of macrophages to these bacteria and significantly enhances the production of pro-inflammatory cytokines – interleukin (IL) 6, IL-1β and tumour necrosis factor alpha (TNF-α). In contrast, galectin-9 did not bind peptidoglycan (PGN), which forms the cell wall of Gram-positive bacteria. Moreover, galectin-9 associated with cellular surfaces (studied in primary human embryonic cells) was not involved in the interaction with bacteria or bacterial colonisation. However, galectin-9 expressed on the surface of primary human embryonic cells, as well as soluble forms of galectin-9, were able to target T lymphocytes and caused apoptosis in T cells expressing granzyme B. Furthermore, “opsonisation” of T cells by galectin-9 led to the translocation of phosphatidylserine onto the cell surface and subsequent phagocytosis by macrophages through Tim-3, the receptor, which recognises both galectin-9 and phosphatidylserine as ligands.

Galectin-9 是半乳糖凝集素家族中的一员，它首先被鉴定为与含有 β-半乳糖苷的碳水化合物特异性结合。Galectin-9 在进化过程中是保守的，最近的证据表明它参与了对细菌感染的先天免疫反应以及抑制 T 细胞和自然杀伤细胞的细胞毒性免疫反应。然而，galectin-9 这种不同免疫功能的分子机制仍然很大程度上未知。在这项工作中，我们证实源自巨噬细胞的可溶性半乳凝素 9 通过与形成细胞壁的脂多糖 (LPS) 相互作用与革兰氏阴性菌结合。这种调理作用很可能会干扰细菌的流动性，导致它们被先天免疫细胞吞噬。Galectin-9 依赖性调理作用还促进巨噬细胞对这些细菌的先天免疫反应，并显着增强促炎细胞因子——白细胞介素 (IL) 6、IL-1β 和肿瘤坏死因子 α (TNF-α) 的产生。相比之下，galectin-9 不结合形成革兰氏阳性细菌细胞壁的肽聚糖 (PGN)。此外，与细胞表面相关的半乳糖凝集素 9（在原代人类胚胎细胞中研究）不参与与细菌的相互作用或细菌定植。然而，在人原代胚胎细胞表面表达的 galectin-9 以及可溶形式的 galectin-9 能够靶向 T 淋巴细胞并导致表达颗粒酶 B 的 T 细胞凋亡。此外，