Maturation of the immune system in the fetus and the implications for congenital CMV

Congenital cytomegalovirus (CMV) infection is the most prevalent and consequential congenital infection, among others, that affects approximately 0.6% of all live births worldwide. Timing of maternal infection and maternal immune status largely determine the likelihood of a symptomatic infection. However, recent studies suggest that the fetal immune system, long perceived as naive and immature, may also play a role in deciding the outcome of congenital CMV infection. Here, we review the development of four immune cells most pertinent to CMV control in the human fetus. αβT cells, B cells, natural killer (NK) cells, and γδT cells are all present, mature and partially functional in utero, and are capable of mounting some form of response to congenital CMV infection. Whether this response is negligible, effective, or harmful remains an open question. Expanding our knowledge of normal and abnormal immune development could provide clinicians with more accurate tools for the detection, monitoring, and treatment of congenital CMV infection in fetuses.