Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada; Dalhousie Human Immunology and Inflammation Group, Halifax, Nova Scotia, Canada.
Dalhousie Human Immunology and Inflammation Group, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Allergy Clin Immunol. 2020 Sep;146(3):631-641.e8. doi: 10.1016/j.jaci.2020.01.049. Epub 2020 Feb 15.
The role of breast-feeding in the development of oral tolerance and allergic diseases is controversial, which could be related to variability in milk components. Toll-like receptor 2 (TLR2) is an innate immune receptor implicated in regulating allergic disease development.
We examined whether deficiency of maternal TLR2 affects the normal development of oral tolerance and related immune parameters during lactation in a mouse model.
Heterozygous TLR2 pups from wild-type (WT) or TLR2 dams were fed either by their biologic dam or a dam of the alternate genotype. Development of oral tolerance to ovalbumin, levels of tolerogenic CD103 dendritic cells, and regulatory T (Treg) cells, as well as intestinal permeability, were evaluated in these pups. The levels of key immune mediators in milk from TLR2 and WT mothers were also examined.
Heterozygous TLR2 pups that were born to and nursed by TLR2 dams exhibited impaired oral tolerance. This was prevented by cross-fostering onto WT (TLR2) dams. Impairments included selective elevation in anti-ovalbumin IgE in plasma following immunization, reduced numbers of tolerogenic dendritic cells and Treg cells in the intestinal tract, and increased intestinal permeability. TLR2 deficiency also affected milk content of insulin-like growth factor-1, IFN-γ, IL-6, and IL-13.
Our results underline a critical role for TLR2 in regulating milk components that are essential for development of oral tolerance in early life and demonstrate the importance of considering the immune status of nursing mothers in studies of immune development and responses.
母乳喂养在口腔耐受和过敏性疾病发展中的作用存在争议，这可能与乳汁成分的可变性有关。Toll 样受体 2（TLR2）是一种先天免疫受体，与调节过敏性疾病的发展有关。
我们研究了 TLR2 缺乏是否会影响哺乳期间母鼠模型中口腔耐受的正常发展和相关免疫参数。
野生型（WT）或 TLR2 母鼠的杂合 TLR2 幼崽由其亲生母鼠或另一基因型的母鼠喂养。在这些幼崽中评估了对卵清蛋白的口服耐受性、诱导性 CD103 树突状细胞和调节性 T（Treg）细胞的水平以及肠道通透性。还检查了 TLR2 和 WT 母亲乳汁中关键免疫介质的水平。
出生并由 TLR2 母鼠哺乳的杂合 TLR2 幼崽表现出口服耐受性受损。这种情况通过交叉寄养到 WT（TLR2）母鼠而得到预防。受损包括免疫后血浆中抗卵清蛋白 IgE 的选择性升高、肠道中诱导性树突状细胞和 Treg 细胞数量减少以及肠道通透性增加。TLR2 缺乏还影响了乳汁中胰岛素样生长因子-1、IFN-γ、IL-6 和 IL-13 的含量。
我们的结果强调了 TLR2 在调节乳汁成分中的关键作用，这些成分对于生命早期口腔耐受的发展至关重要，并证明在研究免疫发育和反应时，考虑哺乳母亲的免疫状态非常重要。
