IgA-mediated control of host-microbial interaction during weaning reaction influences gut inflammation

ABSTRACT

The mechanisms of how host-microbe mutualistic relationships are established at weaning contingently upon B-cell surveillance remain inadequately elucidated. We found that CD138⁺ plasmacyte (PC)-mediated promotion of IgA response regulates the symbiosis between Bacteroides uniformis (B. uniformis) and the host during the weaning period. The IgA-skewed response of CD138⁺ PCs is essential for B. uniformis to occupy a defined gut luminal niche, thereby fostering stable colonization. Furthermore, B. uniformis within the natural gut niche was perturbed in the absence of IgA, resulting in exacerbated gut inflammation in IgA-deficient mice and weaned piglets. Thus, we propose that the priming and maintenance of intestinal IgA response from CD138⁺ PCs are required for host-microbial symbiosis, whereas the perturbation of which would enhance inflammation in weaning process.

Graphical abstract

KEYWORDS:

• Weaning reaction
• gut inflammation
• bacteroides uniformis
• CD138⁺ plasmacyte
• IgA-coated bacteria

Acknowledgments

The authors would like to thank Jinyao Chen and Qiong Huang in the Core Facilities, Zhejiang University School of Medicine for their technical supports. The authors thank Yunqin Li and Li Xie in the Bio-ultrastructure analysis Lab of Analysis Center of Agrobiology and Environmental Sciences (ACAES), Zhejiang University for their technical supports.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

H.F.W. and W.J.T. were involved in every aspect of this study, including the discovery, conceptualization, experimentation, data analysis, and MS preparation; H.F.W. Y.S.W., Z.X.N., K.W.H., and W.J.T. performed experimentation and data analysis; H.F.W. and X.M.L., and W.J.T. contributed to the conceptual, data analysis, and writing components of this study.

Data availability statement

The raw sequencing data have been deposited in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) repository with accession number PRJNA970096 and PRJNA974859. Source data are provided with this article. R markdown scripts enabling the analysis for data are uploaded at https://github.com/Tangwenjie34 and https://github.com/yusenWei. Specific codes are accessible from the authors. All database and detailed description of the methods are available in the main text or the supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2323220

Additional information

Funding

This study was supported by grant from the National Natural Science Foundation of China 32372891 (to H.F.W.), the Key Research and Development Program of China 2022YFD1300602 (to H.F.W.), and the Science and Technology Program of Zhejiang Province 2022C04034 (to H.F.W.).