Kaori Sakamoto, PhD, DVM

When a person inhales a germ, frontline immune system cells called alveolar macrophages normally digest it, protecting the lungs. But that does not happen when a person inhales Mycobacterium tuberculosis (Mtb), the germ that causes TB. This allows Mtb to stay alive in the lung and cause infection.

"Much of the basic science of TB research is centered around how Mtb manages to evade degradation within macrophages," says Kaori Sakamoto, PhD, DVM. "Some of the mechanisms of this process have been determined, but there are still many unanswered questions."

With a Biomedical Research Grant from the American Lung Association, Dr. Sakamoto is studying a receptor called MARCO that is found on the macrophage surface, to understand its role in tuberculosis infection.

In an earlier study, Dr. Sakamoto collaborated on a study that screened people with active TB and the uninfected people who lived with them. The researchers noticed that a variation in the MARCO gene was more often present in people with active TB. "It was never known that MARCO played a role in TB before," she says. "That opened up a new avenue for us, which was very exciting." In another study, she found that MARCO binds to a component of the cell wall of Mtb that is important in TB.

"It was never known that MARCO played a role in TB before. That opened up a new avenue for us which was very exciting."

Dr. Sakamoto and her collaborator, Dr. Dawn Bowdish of McMaster University, found that a genetic variation in the MARCO gene causes a shortened version of MARCO, called MARCOII, which is associated with susceptibility to TB. Dr. Sakamoto will take cells that don't normally produce MARCO, and inject them with genetic material to force them to produce either MARCO or MARCOII. She will then compare the two versions to see whether there are differences in binding, uptake, or macrophage responses to Mtb. "We hope this will help us understand why the shortened version of MARCO is associated with susceptibility to TB at the cellular and molecular levels," she says. "If we can figure out what role MARCO plays in susceptibility to TB, there may be a potential to use this information to prevent TB infection. We also may be able to target MARCO to treat infection," she says.

She notes that it is possible that MARCOII may play a role in other lung diseases in addition to TB. "Our research may elucidate what role MARCO could be playing in these other diseases," she says.