Pamela Odorizzi and colleagues have discovered that human fetal immune cells can proliferate in response to malaria infection in pregnant women, a finding that helps to demystify fetal immunity and potentially has implications for malaria control programs. Malaria, one of the most widespread and costly infectious diseases, frequently infects pregnant women and accumulates in the placenta, resulting in what is known as placental malaria (PM). PM and other forms of pregnancy-associated malaria can cause complications such as low birth weight and are responsible for up to 100,000 deaths worldwide each year. Previous research has indicated that foreign molecules from the malaria parasite could trigger responses from fetal T cells, but the extent of fetal responses against malaria and other diseases remain unknown. To better understand the impact of malaria exposure on the fetal immune system, the authors studied T cells in cord blood from 182 Ugandan infants who were born to mothers with and without PM. Infants born to mothers with PM harbored higher levels of memory fetal T cells and T cells expressing inflammatory molecules, which proliferated in response to malaria antigens. The researchers then followed the same children until two years of age and observed that infants who displayed a higher frequency of T cells due to PM exposure had a 70% lower incidence of clinical malaria compared to infants with lower T cell frequencies, suggesting that PM exposure could generate protection against malaria in childhood. Future studies should assess the nature and durability of this protective effect, the authors say.