The impact of differential antiviral immunity in children and adults

Key Points The immune response is adapted at all stages of early life to maximize survival. These adaptations during intrauterine and early extrauterine life favour protection against extracellular pathogens, and leave infants particularly vulnerable to intracellular pathogens, such as viruses that are transmitted perinatally. This Review contrasts the disease outcomes of three viral infections that can be transmitted perinatally — namely, HIV, cytomegalovirus (CMV) and hepatitis B virus (HBV) infections — in infants and adults to illustrate the ontogeny of the immune response to virus infections and the impact of the immune differences between early life and adulthood on these as well as other viral infections. Following HIV infection of children, survival is ∼1 year without treatment, compared with ∼10 years in adult infection. In HBV infection, perinatal transmission results in persistent infection in 90% of cases, compared with 5% in adults. Although perinatally acquired persistent HBV infection is usually asymptomatic in childhood, it carries a high risk of cirrhosis and hepatocellular carcinoma developing in adulthood. Perinatally transmitted CMV infection, by contrast, does not typically cause disease in infants, although excretion of the virus is prolonged compared with adults. Congenital CMV infection occurring in the first trimester of pregnancy can cause disease in a minority of infants infected at this time. The immune response in intrauterine and early neonatal life is tolerogenic. This is reflected by the propensity of naive fetal T cells to differentiate into regulatory T cells following stimulation by non-inherited maternal alloantigens, and by the greater capacity of neonatal innate immune cells to produce the anti-inflammatory and immunomodulatory cytokine interleukin-10 (IL-10) following Toll-like receptor stimulation. T helper 1 (T H 1) cell-supporting cytokines — such as type I interferons, interferon-γ and IL-12 — are produced in decreased amounts during childhood, and IL-12 production does not reach adult levels until adolescence. By contrast, T H 17 cell-supporting cytokines, such as IL-6 and IL-23, are increased in neonates compared with adults. The apparent skewing of the immune response in fetal and early neonatal life favours defence against extracellular pathogens, and avoids damaging pro-inflammatory T H 1 cell responses, but at the expense of effective antiviral immune responses. In spite of the effective strategies that exis