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HBV found to mature infant immune systems

Hepatitis B virus exposure in utero boosted immune system maturation among a cohort of neonates born to HBV-positive mothers in a Singapore-led study, according to newly published data in Nature Communications.

“Our work contributes to the understanding of how HBV exposure before birth shapes the global immune response of newborn infants and transforms the way we look at HBV,” Michelle Hong, research fellow at Duke-NUS Graduate Medical School, Singapore,  said in a press release. “Despite causing diseases later in life, HBV might actually be beneficial to humans early in life.”

Antonio Bertoletti

Hong and colleagues, including Antonio Bertoletti, MD, professor in the Emerging Infectious Disease Program at Duke-NUS Graduate Medical School, analyzed immune cells in umbilical cord blood of 20 infants born to Asian mothers who were positive for HBV and compared with cord blood of seven infant controls born from mothers negative for HBV, to determine the impact HBV exposure has on the newborn immune system. A second cohort of Caucasians consisting of eight infants born to HBV-positive mothers was also compared with four infants born to HBV-negative mothers.

Overall, researchers found immunosuppressive cytokine IL-10 production to be lower in the cord blood plasma in the HBV-positive mothers compared with the controls (mean: 1.3 ± 0.7 vs. 9.6 ± 4.2). The cord blood plasma of HBV-positive mothers had a lower presence of pro-inflammatory cytokines, anti-inflammatory cytokine, Th17-related cytokine and neutrophil-related chemokines and growth factors compared with the controls, according to the research.

On the other hand, the cord blood plasma of neonates exposed to HBV produced higher levels of IL-12p40, and in some cases, IFN-a2 than controls. The lower production of IL-10 and pro-inflammatory cytokines in the cord blood plasma was also observed in cord blood monocytes of HBV-positive mothers compared with the controls, indicating that HBV exposure in utero created complex changes in the newborn’s immune system that were not entirely stimulatory in nature but were more in line with an advanced immune maturation state, according to the research.

The cord blood mononuclear cells were further tested against various bacteria, including Escherichia coli and Salmonella typhimurium, and a strong Th1 cytokine signature in the HBV-exposed cord blood immune cells was found compared with the controls, suggesting that HBV exposure in utero increased the production of Th1 cytokines toward unrelated pathogen challenge in vitro, according to the research.

 “We demonstrated here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro,” the researchers wrote.

The researchers further state: “Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero.” – by Melinda Stevens 

Disclosure: The researchers report no relevant financial disclosures.