Microbial biochemicals have been indicated as the primary stimulators of innate immunity, the first line of the body’s defence against infections. However, the influence of topological features on a microbe’s surface on immune responses remains largely unknown. Here we demonstrate the ability of TiO₂ microparticles decorated with nanospikes (spiky particles) to activate and amplify the immune response in vitro and in vivo. The nanospikes exert mechanical stress on the cells, which results in potassium efflux and inflammasome activation in macrophages and dendritic cells during phagocytosis. The spiky particles augment antigen-specific humoral and cellular immune responses in the presence of monophosphoryl lipid A and elicit protective immunity against tumour growth and influenza viral infection. The study offers insights into how surface physical cues can tune the activation of innate immunity and provides a basis for engineering particles with increased immunogenicity and adjuvanticity.

微生物生化物质已被证明是先天免疫的主要刺激物，是人体抵抗感染的第一道防线。但是，微生物表面拓扑特征对免疫反应的影响仍然未知。在这里，我们展示了TiO ₂的能力纳米钉（尖峰颗粒）修饰的微颗粒，可在体内和体外激活和增强免疫反应。纳米钉在细胞上施加机械应力，从而在吞噬作用期间导致巨噬细胞和树突状细胞的钾外流和炎症小体活化。在单磷酰基脂质A存在的情况下，刺突颗粒增强了抗原特异性的体液和细胞免疫反应，并引发了针对肿瘤生长和流感病毒感染的保护性免疫。该研究提供了关于表面物理线索如何调节固有免疫力激活的见解，并为工程化具有增强的免疫原性和佐剂性的颗粒提供了基础。