Sexually transmitted infections (STIs) have a major impact on women’s health, as they can cause inflammation of the genital tract, infertility or even cancer. In addition, having an infection or alterations in the microbiota, such as bacterial vaginosis, in the genital tract increases the risk of acquiring other STIs, such as HIV. A study led by the Infectious Diseases group at the Vall d’Hebron Research Institute (VHIR) has identified an immunological mechanism that explains this phenomenon and lays the foundations for defining new therapeutic strategies. The results of the study, mainly funded by La Marató de 3Cat, have been published in the journal Mucosal Immunology.

To study this mechanism, the team analysed cervicovaginal and blood samples from patients with different inflammatory conditions in the genital tract. At Drassanes-Vall d’Hebron, samples were obtained from patients with Chlamydia trachomatis, bacterial vaginosis or co-infections, while at the Hospital’s Department of Gynaecology and Obstetrics, samples were included from patients with human papillomavirus infection, as well as from healthy women.

Specifically, the analyses focused on a type of myeloid cells of the immune system associated with suppression and control of the immune response. This type of cell has been widely studied in the field of cancer, as it plays a role in reducing the immune response needed to eliminate tumours, but it may also help the body to control inflammatory situations in order to prevent damage to its own tissues. Given that STIs stimulate the secretion of factors that could contribute to the development of these cells, and that their role in the genital tract and in the control of STIs is unknown, the group undertook this study.

IL-1β increases myeloid cells that promote immunosuppression

The team identified that, in the genital tract of women with inflammation or infections such as those caused by chlamydia, these myeloid cells increase and are responsible for reducing the immune response. “If the immune response is reduced, infections take longer to resolve and vulnerability to new infections also increases”, highlights Dr. Meritxell Genescà, principal investigator of the VHIR Infectious Diseases group, who led the study.

In addition, the researchers found that an inflammatory molecule promotes the development of myeloid cells: the cytokine IL-1β. “IL-1β is normally secreted during infection to activate inflammatory cells that fight the microorganism. However, if levels remain elevated over a sustained period, it favours the appearance of these myeloid cells in the genital tract and produces the opposite effect, immunosuppression”, explains Dr. Daan K.J. Pieren, who worked on the study as a researcher in the VHIR Infectious Diseases group.

The results obtained from patient samples were confirmed in experiments carried out using a cervical tissue model. For example, the team observed that when the tissue was exposed in the laboratory to infectious chlamydia particles, IL-1β and suppressive myeloid cells also increased. These cells also developed when IL-1β was directly added to the tissue, confirming the relationship between the cytokine and these suppressive cells.

The researchers highlight that these changes were observed only locally in the genital tract, but not in the blood. This underlines the need to detect certain infections directly in genital tract samples in order to achieve an accurate diagnosis, as immunological alterations are not evident in blood.

“Understanding these mechanisms lays the foundations for developing new therapeutic strategies in the future, alternative or complementary to antibiotics, such as reducing IL-1β in the female genital tract in contexts of sustained inflammation. In this way, the activity of the immune system would be increased so that it can eliminate the infection and also prevent others”, states Dr. Genescà.

The study, led by the VHIR Infectious Diseases group, was carried out in collaboration with the Drassanes-Vall d’Hebron International Health and Communicable Diseases Centre, the VHIR Microbiology, Translational Immunology and Clinical Biochemistry, Drug Delivery and Therapy groups, and the Hospital Universitari Vall d’Hebron Departments of Gynaecology and Obstetrics and Pathological Anatomy.

To find out more details about the study, you can listen to the Mucosal Immunology journal podcast via this link (from minute 13:30 on).