Researchers Identify Source of Inflammation and Tissue Damage in Chlamydia Infections

The investigators concluded that 2 separate immune pathways are key players in the way in which the body deals with chlamydia: one pathway clears the bacteria, while another fuels inflammation and tissue damage.

Harvard Medical School researchers have discovered critical information about inflammation that causes complications in chlamydia infections. The study, conducted in mice, pinpointed the cells responsible for this inflammation. Additionally, the investigators concluded that 2 separate immune pathways are key players in the way in which the body deals with chlamydia: one pathway clears the bacteria, while another fuels inflammation and tissue damage.

The results of the research, published in PNAS, indicate that complications result from the inflammation that occurs when Chlamydia trachomatisis presents in the body and immune cells travel to the source: reproductive organs. However, the investigators concluded that the protective immune cells are not responsible for getting rid of the bacteria; that job falls on a different class of immune cells.

“This is a truly encouraging finding,” said study first author Rebeccah Lijek, PhD, assistant professor of biological science at Mount Holyoke College in a press release. “It means that if 1 class of immune cells is responsible for clearing the infection, while another class of immune cells causes tissue damage and subsequent disease, then we can develop treatments that precision target inflammation without exacerbating bacterial levels.”

To test this, the investigators induced symptoms related to chlamydia in humans, in the mice, a success that was unique to this study. Postinfection, the team analyzed the reproductive tissue of the mice to identify the presence of different classes of immune cells. From this point, they were able to determine that neutrophils were the cell class that responded to the bacterium immediately by traveling to the reproductive organs, causing inflammation. The investigators then used an antibody to remove only the neutrophil cells. The results indicated that the mice without neutrophils did not experience tissue damage.

The researchers continued to analyze the infection a week after the bacterium became present in the body. Their observations indicated that in the urogenital tract, there were elevated levels of 2 classes of T cells, which are known to destroy pathogens. The general-assignment, bystander T cells cause inflammation and chlamydia-specific T cells that evolve in response to the presence of chlamydia. This is an important conclusion that answers a question from previous research regarding whether or not chlamydia-specific T cells also cause inflammation.

In order to determine why cells induce inflammation to urogenital tissue bacterium, the research team analyzed more than 700 genes associated with producing inflammation. These genes are responsible for releasing proteins known as chemokines which signal immune cells to travel to the infection site. The investigators found that a trio of chemokines—CXCL 9, 10, 11, known to also have a presence in rheumatoid arthritis and inflammatory bowel disease—had elevated levels.

The final step of the research consisted of the investigators using a chemical compound to block the chemokines causing inflammation. The mice that received the treatment had reduced levels of the bystander T cells and reduced inflammation. These improvements occurred without affecting bacterial levels.

Currently, clinical trials are exploring compounds to reduce inflammation caused by chemokines CXCL 9,10,11 in inflammatory bowel disease. The investigators suggest that similar investigations should occur in the future to treat inflammation from chlamydia infections.