A study by Stanford scientists sheds new light on immune responses to genital Chlamydia trachomatis infection, and may also help inform the development of vaccines that protect against this bacterium.

Chlamydia trachomatis is an obligate intracellular bacterial parasite, meaning it can't replicate outside its host cell. Infecting about 130 million individuals annually, it is the most common sexually transmitted bacterium, says Thomas L. Cherpes, DVM, MD, principal investigator of the new study. In the United States, more than 1.5 million cases were reported to the Centers for Disease Control and Prevention in 2015. The actual number of cases are likely even higher, as Chlamydia infection is usually asymptomatic. While most Chlamydia infections in women are resolved without negative impact, when this bacterium invades the upper genital tract it can cause pelvic inflammatory disease, fallopian tube damage, and infertility.

Four years prior, Cherpes and colleagues reported that genital Chlamydia infection of women generates an inflammatory response called Type 2 immunity. This immune response was better known to dampen inflammation and promote tissue repair during chronic infection with extracellular pathogens such as flatworms, says Rodolfo Vicetti Miguel, MD, the study’s first author. While Chlamydia is an intracellular pathogen, the investigators speculated that the robust Type 2 immunity seen in Chlamydia-infected women may similarly serve to promote repair of infected genital tissue.

The researchers used a mouse model to test this idea. “Mice do not precisely model the human response to infection, but we were able to show Type 2 immunity prevents Chlamydia from causing widespread upper genital tract damage,” says Cherpes, an assistant professor of comparative medicine.

The work, appearing in the Proceedings of the National Academy of Science, also uncovered that the key player in the Type 2 immune response to Chlamydia are eosinophils. These white blood cells are part of the innate immune response, already shown to promote muscle regeneration, reduce liver damage, and stimulate intestinal tissue repair in other experimental systems. “Our current findings confirm and extend these observations, identifying eosinophils as essential for repairing upper genital tract tissue after infectious insult,” says a third study investigator, Nirk Quispe Calla, MD.

Study authors further speculate their findings could shift current thinking about Chlamydia vaccine development. The World Health Organization prioritized Chlamydia vaccine development because of the sizeable impact of the disease on women globally, but most Chlamydia research efforts have focused on building vaccines to induce more pro-inflammatory Type 1 immune responses.

“Understanding the important human host responses to Chlamydia appears to be a moving target,” Vicetti Miguel says. “While Type 1 immunity induces chlamydial clearance, our work indicates Chlamydia vaccines may also need to generate Type 2 immune responses that promote wound healing. This could help prevent repetitive sexual transmission of the bacterium from eliciting tissue inflammation that damages vital genital tract anatomy.”

Because of the importance placed on developing Chlamydia vaccines for women that are both effective and safe, study investigators plan to further explore current findings in clinic studies and in other animal models.

Image courtesy of Thomas Cherpes