TORCH infections at the maternal-fetal placental transmission: an overview of multi-omics, pathogenesis and innate immune defense

The maternal-fetal interface represents a dynamic immunological frontier where pregnancy outcomes are determined by the delicate balance between host defense and microbial pathogenesis. Vertical transmission of pathogens across the placental barrier can lead to devastating consequences including fetal loss, stillbirth, prematurity, and congenital anomalies. The classic TORCH acronym encompasses Toxoplasma gondii, Other agents, Rubella virus, Cytomegalovirus, and Herpes simplex virus, though emerging viruses including Zika virus and SARS-CoV-2 have expanded this spectrum. This review synthesizes current understanding of molecular mechanisms underlying vertical transmission, emphasizing the placenta's multi-layered defense system encompassing the syncytiotrophoblast physical barrier, specialized decidual immune cell populations including decidual natural killer cells and macrophages, and constitutive antimicrobial signaling pathways focusing on the placenta's multi-layered defense system encompassing the syncytiotrophoblast physical barrier, specialized decidual immune cell populations including decidual natural killer cells and macrophages, and constitutive antimicrobial signaling pathways. Concurrently, we examine pathogen strategies to subvert these defenses through receptor manipulation, immune evasion, and intracellular replication niches. A major focus is dedicated to the impact of proteomics and single-cell multi-omics in deconvoluting the host-pathogen interactome and identifying biomarkers of fetal injury. Recent seroprevalence studies demonstrate that younger women represent the most susceptible population to acute TORCH infections, highlighting the need for targeted screening programs. This synthesis provides a framework for developing precision diagnostics and targeted interventions to prevent vertical transmission and reduce the global burden of congenital infections.