Cervical epithelial cells are far from passive bystanders in the body’s immune system. New research shows they actually play an active and highly coordinated role in detecting and fighting infections. That’s the conclusion of an international research team led by Associate Professor Cindrilla Chumduri from Aarhus University, and now published in the journal Science Advances.

Using patient-derived 3D mini-organs, so-called organoids, and single-cell mapping technologies, the team has, for the first time, shown how distinct epithelial cell types in the cervix detect, respond to, and help neutralize infections. Importantly, the study demonstrates that these organoids faithfully recapitulate native human cervical tissue at single-cell resolution, making them powerful discovery platforms for infections, cancer and regenerative biology.

“We’ve demonstrated that the cervix is not just a physical barrier but a truly immunocompetent tissue that orchestrates complex defense mechanisms,” says Cindrilla Chumduri, associate professor at the Department of Biological and Chemical Engineering at Aarhus University.

A multilayered immune response

The researchers focused particularly on chlamydia, the world’s most common bacterial STI. Using single-cell RNA sequencing, they mapped the gene activity of thousands of individual cells in the organoids to reveal their role in immune defense.
The study found that various epithelial cells collaborate in a highly organized defense network. Within each region, specialised epithelial subtypes take on distinct tasks, such as repair, regeneration, or immune amplification. The outer ectocervical squamous cells reinforce the tissue barrier, while deeper endocervical columnar cells act as immune signalers, switching on interferon pathways, antimicrobial defenses, and antigen presentation, triggering alarms. Most surprising was that some of the most immune-active cells were never infected themselves.

“The most striking finding was that uninfected cells became the most immunologically active. They picked up distress signals from neighboring cells and initiated a defense response. It shows how incredibly sophisticated our tissues are,” says Postdoc Pon Ganish Prakash, the study’s first author. The team also decoded cellular conversations, revealing how signaling between epithelial subtypes balances defense with repair. Some subtypes acted as hubs, coordinating the activity of their neighbors.

Toward mucosal vaccines and targeted treatments

These discoveries open new opportunities for vaccines and treatments that stimulate the cervix’s local defense system, rather than relying solely on the systemic immune response. This shift could have major implications for preventing STIs and their complications, such as infertility and cervical cancer. “We see huge potential in developing mucosal vaccines that can activate local immunity right at the infection site,” says Cindrilla Chumduri.

The patient-derived organoids also offer a powerful new platform to study how infections like HPV and chlamydia affect cervical tissue over time, and how co-infections may increase disease risks. “Mini-organs are like a window into human tissue. They allow us to test ideas and treatments in highly realistic models, far more accurate than traditional lab methods,” explains Postdoc Naveen Kumar Nirchal, co-author of the study.

Senior Reseacher Rajendra Kumar Gurumurthy adds: “Our findings show that epithelial heterogeneity is essential. Each subtype has its own job in protecting the cervix and preventing spread of infections to upper reproductive organs.” FACTS & PERSPECTIVES

Sexually transmitted infections affect over a billion people globally, increasing the risk of pregnancy complications, infertility, and cancer. This new study offers hope for better prevention and treatment.

The cervix consists of two distinct epithelial regions: the ectocervix (lined with squamous epithelium) and the endocervix (lined with columnar epithelium). Both play distinct roles in defense. The research also challenges traditional assumptions about epithelial cells, showing them to be immunologically active and diverse. These insights may reshape our understanding of mucosal tissue not only in the cervix but also in the gut, respiratory, and urinary tracts.