Helicobacter pylori outer membrane vesicles mediate central tolerance in C57BL/6J mice offspring T cells via maternal-fetal transmission

Outer membrane vesicles (OMVs) released by <i>Helicobacter pylori</i> (<i>H.pylori</i>) can enter the blood circulation of the host and cause extra-gastric lesions such as atherosclerosis and hyperemesis gravidarum. This study aimed to investigate the effect of OMVs released by <i>H.pylori</i> on the development of thymic T cells in offspring mice and its underlying mechanisms. Through experimental observations, we found that <i>H.pylori</i> OMVs were able to cross the placental barrier, leading to a decrease in the number of CD3⁺ and CD4⁺ T cells in the peripheral blood of the offspring mice and a decrease in the response of T cells to <i>H.pylori</i> stimulation. After stimulation with OMVs in T cell positive selection experiments, the expression levels of CHMP5, IKK-β, and NF-κB are up-regulated, and the release of cytokines IL-7, IL-2, IL-4, and IFN-γ is simultaneously increased, whereas in T cell negative selection experiments, the expression of JNK is up-regulated, and the expression of CHMP5 and Bcl-2 is down-regulated in E15-16 fetal thymus organ culture. These results indicate that transmission of <i>H pylori</i> OMVs from mother to fetus might be related to the development of central tolerance in offspring T cells. The underlying mechanism may involve an interaction between the OMVs-stimulated pathway and the TCR pathway, although further research is needed to confirm this hypothesis. The study highlights the importance of preventing <i>H.pylori</i> infection during pregnancy and suggests that the effect of centrally tolerated antigens needs to be considered in vaccine design to maximize prevention.