IgA antibodies play an important role in mucosal immunity. However, there is still no effective way to consistently boost mucosal IgA responses, and the factors influencing these responses are not fully understood. We observed that colonization with the murine intestinal symbiotic protozoan Tritrichomonas musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type C57BL/6 mice. This enhancement was attributed to the accumulation of free arachidonic acid (ARA) in the intestinal lumen, which served as a signal to stimulate the production of antigen-specific mucosal IgA. When ARA was prevented from undergoing its downstream metabolic transformation using the 5-lipoxygenase inhibitor zileuton or by blocking its downstream biological signaling through genetic deletion of the Leukotriene B₄ receptor 1 (Blt1), the T.mu-mediated enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, both T.mu transfer and dietary supplementation of ARA augmented the efficacy of an oral vaccine against Salmonella infection, with this effect being dependent on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral immune response.

IgA抗体在粘膜免疫中发挥重要作用。然而，仍然没有有效的方法来持续增强粘膜 IgA 反应，并且影响这些反应的因素尚未完全了解。我们观察到，小鼠肠道共生原生动物肌毛滴虫( T.mu ) 的定植增强了野生型 C57BL/6 小鼠的抗原特异性粘膜 IgA 反应。这种增强归因于肠腔中游离花生四烯酸 (ARA) 的积累，它作为刺激抗原特异性粘膜 IgA 产生的信号。当使用 5-脂氧合酶抑制剂齐留通或通过基因删除白三烯 B ₄受体 1 ( Blt1 ) 阻断其下游生物信号传导来阻止 ARA 进行下游代谢转化时， T.mu介导的抗原特异性粘膜增强作用IgA 的产生受到抑制。此外， T.mu转移和膳食补充 ARA 都增强了口服疫苗对抗沙门氏菌感染的功效，这种效果依赖于 Blt1。我们的研究结果阐明了将饮食或肠道微生物群的营养物质、宿主脂质代谢和粘膜体液免疫反应联系起来的三重回路。