A family of proteins known as interferon lambdas produced by epithelial cells in the mouth serve to protect humans from viral infection, but the oral bacteria Porphyromonas gingivalis reduces the production and effectiveness of those important frontline defenders.

“Our studies identified certain pathogenic bacterial species, P. gingivalis, which cause periodontal disease, can completely suppress interferon production and severely enhance susceptibility to viral infection,” said Juhi Bagaitkar, assistant professor in the UofL Department of Oral Immunology and Infectious Disease. “These resident oral plaque bacteria play a key role in regulating anti-viral responses.”

Bagaitkar and Richard Lamont, professor and chair of the UofL Department of Oral Immunology and Infectious Disease, led the work, with first author Carlos J. Rodriguez-Hernandez and other colleagues at UofL and at Washington University in St. Louis. The findings were published

The mouth often is a gateway into the body for viruses that infect the gastrointestinal tract and lungs such as SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex and cancer-causing viruses such as human papillomavirus (HPV).

P. gingivalis, a common oral bacterium that causes periodontal disease, has been linked to numerous other diseases, including Alzheimer’s disease and rheumatoid arthritis. Recent clinical studies have shown that immune suppression in patients with periodontitis can enhance susceptibility to HIV, herpes simplex and HPV.

Improved understanding of how interferons provide broad antiviral protection and activate antiviral genes to protect us from viruses, as well as how P. gingivalis compromises their protection, may lead researchers to clinical approaches to increase that protection.

Research at UofL has revealed connections between P. gingivalis and multiple other diseases and conditions, including rheumatoid arthritis, Alzheimer’s disease and esophageal cancer.

Bagaitkar was one of the first junior faculty members whose research was supported by the Center of Biomedical Research Excellence (CoBRE) for research in microorganism disease research funded by the National Institute of General Medical Sciences.

“Billions of cells die daily as a consequence of regular wear and tear, tissue turnover and during an inflammatory response. The body dedicates a significant amount of energy in the specific recognition and uptake of these dead cells via specific pathways,” said Juhi Bagaitkar, PhD, a researcher in the University of Louisville School of Dentistry’s Department of Oral Immunology and Infectious Diseases. “If you don’t bury the dead cells, they can burst open and cause harm, however the underlying mechanisms are incompletely characterized.”

Bagaitkar, along with researchers at Washington University, Indiana University and University of Michigan, recently published a paper in , demonstrating the importance of oxidants in the digestion of apoptotic, or dead cells. 

Specifically, the research uncovers how NADPH-oxidase is activated to generate reactive oxygen species (ROS) in macrophages, a kind of white blood cell that eats dead cells. These cells also are involved in getting rid of viruses and bacteria.

The presence of ROS is critical as its generation drives additional mechanisms involved in the digestion of cellular corpses to perform at an optimal level. This allows the macrophage to complete the digestion process of efferocytosis, meaning “to bury the dead.”

“Independent of their role in microbial killing, we are gaining even greater appreciation of ROS for their huge role in the regulation of host immune response,” Bagaitkar said. “Uncovering this role of ROS in the clearance of dead cells sheds some mechanistic insights on how oxidants function in limiting of host inflammation rather than activating it.

“When our bodies produce too much or too little ROS, we become pre-disposed to autoimmune disease and chronic inflammation. Producing just enough – the optimal level – is what’s needed,” she said.