Galectins at the maternal-fetal interface: shield or gateway to infections?

Pregnancy relies on a tightly regulated immune balance at the maternal-fetal interface, where tolerance toward the semi-allogeneic fetus must coexist with effective defense mechanisms against invading pathogens. In this context, galectins (gals), a family of β-galactoside-binding lectins, play essential roles in placentation, angiogenesis, tissue remodeling, and immune regulation. Beyond their physiological functions, accumulating evidence indicates that these proteins also participate in host-virus interactions, acting either to restrict infection or to facilitate viral attachment, entry, replication, and persistence. In this review, we discuss the structural characteristics, unconventional secretion pathways, and major immunological functions of gal, with particular emphasis on gal-1, gal-3, gal-9 and gal-13, at the maternal-fetal interface. We also summarize the current evidence regarding their involvement in congenital infections caused by cytomegalovirus (CMV), Zika virus (ZIKV), and human immunodeficiency virus (HIV). Available studies indicate that gals modulate key processes, including viral entry, immune cell activation, inflammation, viral persistence, and maternal-fetal transmission, although their specific mechanisms of action within the placenta remain poorly understood. Collectively, the available evidence suggests that gals exert dual and context-dependent functions, acting as critical regulators of the delicate balance between immune tolerance and antiviral defense. A better understanding of these mechanisms may contribute to the identification of novel biomarkers and improve our understanding of the pathogenesis of congenital infections, ultimately leading to better pregnancy outcomes.