Solely HBsAg intrauterine exposure accelerates HBV clearance by promoting HBs-specific immune response in the mouse pups

Abstract

Chronic hepatitis B virus (HBV) infection due to perinatal mother-to-infant transmission (MTIT) remains a serious global public health problem. It has been shown that intrauterine exposure to HBV antigens might account for the MTIT-related chronic infection. However, whether hepatitis B surface antigen (HBsAg) intrauterine exposure affected the offspring’s immune response against HBV and MTIT of HBV has not been fully clarified. In this study, we investigated the effects and the potential mechanisms of the HBsAg intrauterine exposure on the persistence of HBV replication using a solely HBsAg intrauterine exposure mice model. Our results revealed that solely HBsAg intrauterine exposure significantly accelerated the clearance of HBV when these mice were hydrodynamically injected with pBB4.5-HBV1.2 plasmids after birth, which may be due to the increased number of HBs-specific CD8 + T cells and interferon-gamma secretion in the liver of mice. Mechanismly, HBsAg intrauterine exposure activated antigen-presenting dendritic cells, which led to the generation of antigen-specific cellular immunological memory. Our data provide an important experimental evidence for the activation of neonatal immune response by HBsAg intrauterine exposure.

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity

“…Through the research on a mouse model of only HBsAg exposure in utero , Ning et al. came to the first conclusion that, contrary to what others had previously thought, HBeAg played an immunosuppressive effect on the offspring; only HBsAg exposure in utero did not develop the immune tolerance to HBV on the fetus; however, when re-exposed to HBV, the offspring could speed up the elimination of HBV in the body; and this beneficial effect may be related to only HBsAg exposure in utero , which could activate antigen-presenting dendritic cells and then induce an increase of the HB-specific CD8 + T cells and secretion of interferon (IFN)-γ in the hepar of mice ( 62 ). Another research by cord blood analysis also showed that immunity of newborn infants can be beneficially affected due to the HBV-infected state of their Asian mothers; it was mainly manifested as the enhancement of innate immune cell maturation and the increasement of Th1 development, and specially showed that low levels of IL-10 (Th2-related cytokines) and high levels of IL-12p40, IFN-α2 (Th1-related cytokines); importantly, such enhancement effect led to the robust response of the neonatal immune cells when they were exposed in vitro to pathogens that were unrelated to their condition, and the pathogens were Pseudomonas aeruginosa , Salmonella typhimurium , uropathogenic, Escherichia coli , Acinetobacter baumanii , and Listeria monocytogenes ; however, this beneficial effect cannot be demonstrated in the baby Caucasian HBV-infected mother’s delivery, which was explained by different HBV genotypes; patients of Asian descent had HBV genotypes B/C, while patients of Caucasian descent had HBV genotype D ( 63 ).…”