CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
Bio Bharati Life Science Pvt. Ltd., Kolkata, West Bengal, India.
mSphere. 2024 Sep 25;9(9):e0020424. doi: 10.1128/msphere.00204-24. Epub 2024 Aug 14.
We investigated the influence of a Wnt5A-gut microbiota axis on gut B-cell repertoire and protection from infection, having previously demonstrated that Wnt5A in association with gut commensals helps shape gut T-cell repertoire. Accordingly, Wnt5A heterozygous mice, which express less than wild-type level of Wnt5A, and their isolated Peyer's patches (PPs) were studied in comparison with the wild-type counterparts. The percentages of IgM- and IgA-expressing B cells were quite similar in the PP of both sets of mice. However, the PP of the Wnt5A heterozygous mice harbored significantly higher than wild-type levels of microbiota-bound B cell-secreted IgA, indicating the prevalence of a microbial population therein, which is significantly altered from that of wild-type. Additionally, the percentage of PP IgG1-expressing B cells was appreciably depressed in the Wnt5A heterozygous mice in comparison to wild-type. Wnt5A heterozygous mice, furthermore, exhibited notably higher than the wild-type levels of morbidity and mortality following infection with , a common gut pathogen. Differences in morbidity/mortality correlated with considerable disparity between the PP-B-cell repertoires of the -infected Wnt5A heterozygous and wild-type mice, in which the percentage of IgG1-expressing B1b cells in the PP of heterozygous mice remains significantly low as compared to wild-type. Overall, these results suggest that a gut Wnt5A-microbiota axis is intrinsically associated with the maintenance of gut B-cell repertoire and protection from infection.IMPORTANCEAlthough it is well accepted that B cells and microbiota are required for protection from infection and preservation of gut health, a lot remains unknown about how the optimum B-cell repertoire and microbiota are maintained in the gut. The importance of this study lies in the fact that it unveils a potential role of a growth factor termed Wnt5A in the safeguarding of the gut B-cell population and microbiota, thereby protecting the gut from the deleterious effect of infections by common pathogens. Documentation of the involvement of a Wnt5A-microbiota axis in the shaping of a protective gut B-cell repertoire, furthermore, opens up new avenues of investigations for understanding gut disorders related to microbial dysbiosis and B-cell homeostasis that, till date, are considered incurable.
我们研究了 Wnt5A-肠道菌群轴对肠道 B 细胞 repertoire 的影响及其对感染的保护作用，因为此前我们的研究表明，Wnt5A 与肠道共生菌结合有助于塑造肠道 T 细胞 repertoire。因此，我们研究了 Wnt5A 杂合子（表达的 Wnt5A 水平低于野生型）及其分离的派尔集合淋巴结（PP），并与野生型进行了比较。两组小鼠的 PP 中 IgM 和 IgA 表达 B 细胞的百分比非常相似。然而，Wnt5A 杂合子的 PP 中，与野生型相比，结合微生物的 B 细胞分泌的 IgA 水平显著升高，这表明其中存在一种明显改变的微生物群体。此外，与野生型相比，Wnt5A 杂合子的 PP 中 IgG1 表达 B 细胞的百分比明显降低。此外，与野生型相比，感染 后，Wnt5A 杂合子的发病率和死亡率显著升高， 是一种常见的肠道病原体。发病率/死亡率的差异与感染后 Wnt5A 杂合子和野生型小鼠 PP-B 细胞 repertoire 之间的显著差异相关，其中杂合子小鼠的 PP 中 IgG1 表达的 B1b 细胞的百分比仍然明显低于野生型。总之，这些结果表明，肠道 Wnt5A-菌群轴与肠道 B 细胞 repertoire 的维持和感染的保护密切相关。
这项研究的重要意义在于，它揭示了一种称为 Wnt5A 的生长因子在保护肠道 B 细胞群体和微生物群方面的潜在作用，从而保护肠道免受常见病原体感染的有害影响。此外，证明了 Wnt5A-菌群轴在塑造保护性肠道 B 细胞 repertoire 中的作用，为理解与微生物失调和 B 细胞动态平衡相关的肠道疾病开辟了新的研究途径，迄今为止，这些疾病被认为是无法治愈的。
