Cytomegaloviruses and Macrophages—Friends and Foes From Early on?

Starting at birth, newborn infants are exposed to numerous microorganisms. Adaptation of the innate immune system to them is a delicate process, with potentially advantageous and harmful implications for health development. Cytomegaloviruses (CMVs) are highly adapted to their specific mammalian hosts, with which they share millions of years of co-evolution. Throughout the history of mankind, human CMV has infected most infants in the first months of life without overt implications for health. Thus, CMV infections are intertwined with normal immune development. Nonetheless, CMV has retained substantial pathogenicity following infection in utero or in situations of immunosuppression, leading to pathology in virtually any organ and particularly the central nervous system (CNS). CMVs enter the host through mucosal interfaces of the gastrointestinal and respiratory tract, where macrophages (MACs) are the most abundant immune cell type. Tissue MACs and their potential progenitors, monocytes, are established target cells of CMVs. Recently, several discoveries have revolutionized our understanding on the pre- and postnatal development and site-specific adaptation of tissue MACs. In this review, we explore experimental evidences and concepts on how CMV infections may impact on MAC development and activation as part of host-virus co-adaptation.