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1.08.2020

Bronchial Cells Play a Key Role in Immune Response

Mycobacteria are antibiotic-resistant microbes that are often implicated in lung infections. To fight them, the body activates interferon and other immune proteins, but scientists weren’t sure how the process worked.

Now, in a study published in the journal Frontiers in Immunology, researchers from the Miller School of Medicine and Cleveland Clinic have mapped out interactions between Mycobacterium abscessus (MAB) particles and normal human bronchial epithelium (NHBE) — the cells that line lung passageways. The research team found that, when encountering MAB particles, NHBE cells help initiate an immune response. This new understanding could eventually lead to better treatments.

“We developed systems to mimic what is happening to people with mycobacteria disease,” said Mehdi Mirsaeidi, M.D., M.P.H., assistant professor in the Division of Pulmonary and Critical Care, who was senior author on the study. “We work on macrophages, lymphocytes, neutrophils and other immune cells. However, we believe epithelial cells should be recognized as a part of the immune system.”

To understand how NHBE cells mediate immunity, Dr. Mirsaeidi and colleagues created two models. The first was a chip that allowed them to study the interactions between NHBEs and the microparticles, which were made from MAB cell walls.

The results showed exposing bronchial epithelial cells to the MAB microparticles activated genes associated with a powerful immune response. RNA tests showed 1,759 genes were expressed differently based on their MAB exposure. In particular, genes associated with the immune protein cytokine interferon 1 were boosted significantly.

“We exposed these specific microparticle antigens to bronchial epithelial cell interior layers and they reacted like immune cells,” Dr. Mirsaeidi said. “They produced different cytokines and proteins that can attract the immune system, including type one interferon.”

The researchers also tested the microparticles in an animal model, which helped them track how NHBEs influenced the immune response.

“We learned that, when epithelial cells get exposed to these specific antigens, they’re going to interact with immune cells,” Dr. Mirsaeidi said. “We showed that type one interferon got a significant increase in immune cells in the lung. The epithelial cells initiated it, and then other parts of the immune system responded.”

This study provides important new insights into how innate immunity operates. The scientists were particularly impressed they could induce an immune response with microparticles from the bacterial cell walls alone — no actual bacteria were used. In other words, the epithelial cells were sensitive to these molecules and generated an immune response when they encountered them.

The researchers will continue to dissect these pathways to understand the different proteins that help activate interferon and other inflammatory proteins.

“Now that we understand that epithelial cells can orchestrate an immune response — based solely on bacterial surface proteins — it could give us new tools to modulate immunity,” Dr. Mirsaeidi said.

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