A mouse protozoan boosts antigen-specific mucosal IgA responses in a specific lipid metabolism- and signaling-dependent manner
Yanbo Kou, Shenghan Zhang, Junru Chen, Yusi Shen, Zhiwei Zhang, Haohan Huang, Yu‐Lu Ma, Yaoyao Xiang, Longxiang Liao, Junyang Zhou, Wanpeng Cheng, Yuan Zhou, Huan Yang, Zhuanzhuan Liu, Yanxia Wei, Hui Wang, Yugang Wang
Abstract
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. Immunoglobulin A (IgA) is an important part of the mucosal immune response. Here, the authors show that an intestinal commensal protist can enhance mucosal IgA production upon vaccination and that this involves the accumulation of free arachidonic acid in the intestinal lumen.