Antibody-dependent enhancement (ADE) of infectious disease is a phenomenon whereby host antibodies increase the severity of an infection. It is well established in viral infections but ADE also has an underappreciated role during bacterial, fungal and parasitic infections. ADE can occur during both primary infections and re-infections with the same or a related pathogen; therefore, understanding the underlying mechanisms of ADE is critical for understanding the pathogenesis and progression of many infectious diseases. Here, we review the four distinct mechanisms by which antibodies increase disease severity during an infection. We discuss the most established mechanistic explanation for ADE, where cross-reactive, disease-enhancing antibodies bound to pathogens interact with Fc receptors, thereby enhancing pathogen entry or replication, ultimately increasing the total pathogen load. Additionally, we explore how some pathogenic antibodies can shield bacteria from complement-dependent killing, thereby enhancing bacterial survival. We interrogate the molecular mechanisms by which antibodies can amplify inflammation to drive severe disease, even in the absence of increased pathogen replication. We also examine emerging roles for autoantibodies in enhancing the pathogenesis of infectious diseases. Finally, we discuss how we can leverage these insights to improve vaccine design and future treatments for infectious diseases.

传染病的抗体依赖性增强（ADE）是宿主抗体增加感染严重程度的现象。 ADE 在病毒感染中已得到充分证实，但在细菌、真菌和寄生虫感染中的作用也未被充分认识。 ADE 可能发生在相同或相关病原体的初次感染和再次感染期间；因此，了解 ADE 的潜在机制对于了解许多传染病的发病机制和进展至关重要。在这里，我们回顾了抗体在感染期间增加疾病严重程度的四种不同机制。我们讨论了 ADE 最成熟的机制解释，即与病原体结合的交叉反应、疾病增强抗体与 Fc 受体相互作用，从而增强病原体进入或复制，最终增加病原体总负荷。此外，我们还探讨了一些致病性抗体如何保护细菌免受补体依赖性杀伤，从而提高细菌的存活率。我们探究了抗体放大炎症以驱动严重疾病的分子机制，即使在病原体复制不增加的情况下也是如此。我们还研究了自身抗体在增强传染病发病机制中的新作用。最后，我们讨论如何利用这些见解来改进疫苗设计和未来传染病的治疗。