Placental Barrier–Pathogen Interactions: Cellular Gateways, Immune Crosstalk, and Outcomes in Congenital Disease

The placenta is a uniquely specialized organ that acts as both a physical barrier and an active immunological interface between the mother and fetus. Despite its critical protective role, several pathogens, including Toxoplasma gondii, Trypanosoma cruzi, Plasmodium species, Zika virus, cytomegalovirus, and others are capable of crossing or disrupting the placental barrier, leading to congenital disease. The mechanisms that enable or prevent transplacental transmission involve complex interactions between trophoblast lineages, metabolic and immunological pathways, and pathogen-driven remodeling of the maternal–fetal interface. Emerging technologies, including single-cell and spatial multi-omics, advanced imaging, and computational modeling, have recently uncovered new aspects of trophoblast biology, immune crosstalk, and pathogen behavior in the placental environment. However, a comprehensive synthesis of how cellular gateways and immunological signals shape congenital infection susceptibility remains lacking.

This Research Topic aims to provide a platform for researchers to present their latest findings on how pathogens engage with the placental barrier and how these interactions influence fetal risk and disease outcomes. The collection will emphasize the distinct cellular entry routes available to pathogens, including different subpopulations of trophoblasts, such as syncytiotrophoblast, cytotrophoblast and extravillous trophoblast, and how infection affects trophoblast differentiation, barrier integrity, and placental function. We also seek studies uncovering pathogen-induced metabolic rewiring, the roles of extracellular vesicles in communication and immune modulation, and the contribution of complement and antibody effector functions at the maternal–fetal interface. Together, these insights can clarify the regulatory mechanisms that determine whether the placenta restricts or permits infection and inform strategies to prevent congenital transmission.

We welcome papers addressing the following themes, including but not limited to:

-Cellular and molecular mechanisms of pathogen entry across the placental barrier (syncytiotrophoblast vs. cytotrophoblast vs. extravillous trophoblast).
-Impact of infection on trophoblast lineage specification, differentiation, and barrier integrity.
-Metabolic rewiring of trophoblasts and placental tissues during congenital infection.
-Roles of extracellular vesicles in immune communication, pathogen spread, and placental remodeling.
-Complement pathways, Fc-mediated antibody functions, and innate immune responses at the maternal–fetal interface.
-Biomarkers predicting placental dysfunction, fetal exposure, or risk of congenital disease.
-Experimental and computational models of maternal–fetal transmission, including organoids, ex vivo explants, live imaging, and in silico modeling.
-Co-infection contexts and comparative analyses across parasitic, viral, and bacterial congenital pathogens.

This Research Topic aims to advance our understanding of placental barrier–pathogen interactions and promote the development of innovative diagnostic, preventive, and therapeutic strategies for congenital infections.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• Methods
• Mini Review
• Original Research
• Perspective
• Review
• Systematic Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• Methods
• Mini Review
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: cellular entry routes, syncytiotrophoblast infection, cytotrophoblast infection, extravillous trophoblast invasion, trophoblast lineage specification, placental barrier integrity, metabolic rewiring, extracellular vesicles, complement activation, FcRn-med

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.