2. Academic Validation
  3. A mouse protozoan boosts antigen-specific mucosal IgA responses in a specific lipid metabolism- and signaling-dependent manner

A mouse protozoan boosts antigen-specific mucosal IgA responses in a specific lipid metabolism- and signaling-dependent manner

  • Nat Commun. 2024 Sep 10;15(1):7914. doi: 10.1038/s41467-024-52336-z.
Yanbo Kou # 1 2,  Shenghan Zhang # 1 2 3,  Junru Chen 1 2,  Yusi Shen 1 2,  Zhiwei Zhang 1 2,  Haohan Huang 1 2,  Yulu Ma 1 2,  Yaoyao Xiang 1 2,  Longxiang Liao 1 2,  Junyang Zhou 1 2,  Wanpeng Cheng 1 2,  Yuan Zhou 4,  Huan Yang 4,  Zhuanzhuan Liu 1 2,  Yanxia Wei 1 2,  Hui Wang 1 2,  Yugang Wang 5 6
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
  • 2 Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China.
  • 3 Department of Central Laboratory, Xuzhou Central Hospital, Xuzhou, China.
  • 4 Xuzhou Key Laboratory of Laboratory Diagnostics, Medical Technology School, Xuzhou Medical University, Xuzhou, China.
  • 5 Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China. wangyg@xzhmu.edu.cn.
  • 6 Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China. wangyg@xzhmu.edu.cn.
  • # Contributed equally.
PMID: 39256385 DOI: 10.1038/s41467-024-52336-z
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.

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