The effect of histone methylation in trained innate immunity of cord blood monocytes in newborn infants of chronic HBV-infected mothers

Abstract

Newborns contract Hepatitis B virus (HBV) through exposure in utero from mothers who are infected with HBV. In newborn infant from chronic HBV-infected mothers, the immune system displays innate immune cell maturation and enhances immune response upon restimulation with unrelated pathogens such as bacteria. This pattern is called “trained immunity” or “innate immune memory”. Trained immunity is regulated by epigenetic programming, especially histone modification. To date, there is not report on the epigenetics to regulate trained immunity in HBV. Therefore, this study investigated the cytokines levels and expression levels of histone modification enzyme genes in HBV-exposed cord blood monocytes. Moreover, we demonstrated histone modifications at position H3K4me3 that regulated IL-12p40, IL-6, IL-10, TNF-a, and IL-1b genes in monocytes from HBV-exposed cord blood. The expression of IL-12p40 was significantly higher in HBV-exposed cord blood monocytes than healthy cord blood monocytes after restimulation with TLR8 agonist. In addition, mRNA expression of histone modification enzymes was not significantly different between HBV-exposed cord blood monocytes and cord blood monocytes. Moreover, the level of histone methylation at position H3K4me3 of cytokine genes did not support trained immunity in this study. It is likely to be that epigenetic programming through histone modification at position H3K4me3 might be not involved in HBV-trained immunity.