UGA researchers receive NIH grants to study innate immunity to influenza and pneumococcus

By Alec Lee

Balázs Rada, associate professor of infectious diseases and head of the Laboratory of Mucosal Innate Immunity and Neutrophil Biology at UGA, is the principal investigator on two NIH-funded projects totaling $2.3M. Rada and his team will study the body’s innate immune response to influenza and a pneumonia-causing bacterium, Streptococcus pneumoniae, also known as pneumococcus.

Epithelial cells are common in the body. They cover all body surfaces, line body cavities and hollow organs, and make up the largest part of our glands. These cells can also serve a purpose in the human immune system within our airways. A gene called DUOX1 allows these cells to generate reactive oxygen species to destroy foreign invaders and defend the body against bacteria, viruses, and fungi.

The two grants awarded by the National Institute of Allergy and Infectious Diseases will allow Rada to test how effective these cells are in combating the influenza virus and the most common cause of pneumonia, Streptococcus pneumoniae. “It has been proven that this gene is effective against a wide range of microorganisms in the laboratory in a Petri dish, but we hope to confirm its antimicrobial activity and to unravel its mechanism of action in living tissue,” Rada explains.

The first award, an R01 grant, will be distributed over five years and focuses on influenza. Rada will collaborate with co-principal investigator Ralph Tripp, Georgia Research Alliance Eminent Scholar and professor of infectious diseases who is an expert on influenza as well as other respiratory viruses. Together, the team hopes to learn more about the effectiveness of DUOX1 in vivo. Specifically, they are interested in determining the molecular and cellular mechanisms that give epithelial cells their antibacterial and antiviral properties and determine whether airway oxidants are effective in reducing lung disease and viral replication during influenza infection.

The second award, an R21 exploratory grant, has similar goals but a different focus. For two years, Rada and his team will study the effects of this oxidant-generating system against Streptococcus pneumoniae. Influenza sufferers are much more likely to develop pneumonia, and pneumococcus is its leading bacterial cause. When the body is infected with viruses like influenza, the immune system is severely weakened, leaving easy access for other bacteria like pneumococcus to enter the lungs. For this project, Rada will partner with University of Mississippi Medical Center Professor of Microbiology Larry McDaniel, an expert on pneumococcus.

In performing this research, Rada and his team hope to deepen our understanding of how the body fights back against invasion by two particularly dangerous microorganisms. Influenza alone can be a deadly disease, and its danger is only amplified with the risk of co-infection. This study will be the first to see these reactive oxidant-based mechanisms in action against influenza and pneumococcus outside of a test tube. Research of this nature can be beneficial for future understanding of our own immune system and for developing therapies to boost our immune responses against respiratory pathogens.

Rada explains, “As we learn more about the antimicrobial role of these airway oxidants, we gain essential knowledge about the innate immune system of the lung and learn ways to strengthen the immune response to influenza and pneumococcus.”

More information about these projects can be found on the Rada laboratory website.

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