Perinatal depression is an emerging field with questions that remain to be answered, including the underlying
pathogenesis, treatment and counseling. Pregnant women with depression represent a serious risk to themselves due to
negative fetal/obstetrical and neonatal outcomes and to their child with respect to development later in life. The immune
system plays a crucial role in major depression disorder (MDD), and studies indicate that both immune mediators
(cytokines, chemokines) and neuroendocrine hormones cross-talk in MDD. However, the innate immune system is an
unexplored field, and its link with prenatal depression has not been fully explored. The innate immune system is tightly
regulated during early implantation and placentation of the conceptus, and such regulation is crucial for a successful
pregnancy. T lymphocytes, which comprise helper T lymphocytes (Th), and cytotoxic T lymphocytes (CTLs), have been
shown to be abundant at the fetomaternal interface together with the recruitment of different subsets of immune cells
[Natural Killer cells (NK), Dendritic cells (DCs), Macrophages (MΦs)] during decidualization of the endometrium.
Pregnancy is considered to be an inflammatory process in which a Th2 over a Th1 immune response is critical for
allowing the development of the fetal allograft. Stressful stimuli and prenatal infections have been shown to deregulate the
Th1/Th2 balance and are associated with increased production of proinflammatory cytokines and modification of neonatal
immune responses via toll-like receptor (TLR) signaling. The innate immune system could represent a new frontier in
exploring the etiology of several mental disorders, as suggested for schizophrenia. However, it is not clear how the innate
immune system cross-talks with the fetal brain during perinatal depression.