巨噬细胞是先天免疫的关键效应细胞，在疾病发病的免疫平衡中起着至关重要的作用，尤其在肿瘤微环境中。在先前的研究中，我们显示了FimH（大肠杆菌黏附部分）促进了树突状细胞的激活。然而，FimH在巨噬细胞极化中的作用尚未得到充分的研究。在本研究中，我们对FimH对巨噬细胞的潜在影响进行了调查，以及由M2极化为M1巨噬细胞，为整体抗肿瘤效应做出贡献。我们生成了小鼠骨髓源性巨噬细胞和腹腔巨噬细胞以测试FimH在体外的作用。分析了共刺激分子的表达和细胞因子的产生。检查了FimH在B16F10肿瘤中的巨噬细胞的作用。我们发现FimH促进了M1巨噬细胞的激活。此外，FimH极化了由白细胞介素（IL）-4和IL-13诱导的M2巨噬细胞，其极化成M1巨噬细胞依赖于Toll样受体4和髓系分化因子2。此外，FimH重编程了B16黑色素瘤携带小鼠中的肿瘤相关巨噬细胞（TAM）为M1巨噬细胞，并在肿瘤微环境（TME）中促进了炎症反应。此外，FimH促进了人类M1巨噬细胞的激活，并将M2巨噬细胞逆转为M1巨噬细胞。最后，我们发现FimH治疗能通过引起肿瘤相关巨噬细胞的M1极化，增强抗PD-L1抗体的抗癌免疫力。本研究证明了FimH对巨噬细胞激活的潜在作用，负责通过TLR4信号通路将M2巨噬细胞重新极化为M1表型。此外，FimH还能重新编程TME中的TAM极化为M1状态，并增强免疫检查点阻滞的抗肿瘤活性。版权所有 © 2023 张，徐，张，徐和金。

Macrophages are key effector cells of innate immunity and play a critical role in the immune balance of disease pathogenesis, especially in the tumor microenvironment. In previous studies, we showed that FimH, an Escherichia coli adhesion portion, promoted dendritic cell activation. However, the effect of FimH in macrophage polarization has yet to be fully examined. In this study, we investigated the potential effect of FimH on macrophages, as well as the polarization from M2 to M1 macrophages, contributing to the overall antitumor effect.Mouse bone marrow derived macrophages and peritoneal macrophages were generated to test the effect of FimH in vitro. The expression of costimulatory molecules and production of cytokines were analyzed. The effect of FimH in the tumor-associated macrophages was examine in the B16F10-tumor bearing C57BL/6.FimH was found to promote M1 macrophage activation. In addition, FimH polarized M2 macrophages, which were induced by interleukin (IL)-4 and IL-13 into M1 macrophages were dependent on toll-like receptor 4 and myeloid differentiation factor 2. Moreover, FimH reprogramed the tumor-associated macrophage (TAM) into M1 macrophages in B16 melanoma tumor-bearing mice and promoted an inflammatory reaction in the tumor microenvironment (TME). Furthermore, FimH promoted M1 macrophage activation, as well as the reversion of M2 macrophages into M1 macrophages in humans. Finally, FimH treatment was found to enhance the anti-cancer immunity of anti-PD-L1 antibody by the induction of M1 polarization from TAM.This study demonstrated the potential effect of FimH on the activation of macrophages, responsible for the repolarization of M2 macrophages into the M1 phenotype via the TLR4 signaling pathway. Moreover, FimH could also reprogram TAM polarization to the M1 status in the TME, as well as enhance the anti-tumor activity of immune checkpoint blockade.Copyright © 2023 Zhang, Xu, Zhang, Xu and Jin.