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LOUISVILLE, Ky., US: Researchers from the US have recently examined the role that oral microbes play in regulating antiviral responses in the oral cavity. They discovered that proteins produced by oral epithelial cells protect humans against viruses entering the body through the mouth, including SARS-CoV-2, but that oral bacteria can suppress the activity of these cells, thus increasing vulnerability to infection.
The study was led by two researchers from the University of Louisville School of Dentistry, Dr Richard J. Lamont, Delta Dental endowed professor and chair of the Department of Oral Immunology and Infectious Diseases, and Dr Juhi Bagaitkar, associate professor in the department.
Discussing her interest in the study, Dr Bagaitkar told Dental Tribune International that understanding immune responses and how they are manipulated by oral microbes has been a shared interest of the Lamont and Bagaitkar laboratories. She added that this common interest had been the foundation of several collaborative research projects undertaken by the laboratories.
While working on their projects, the researchers noticed that, in comparison with the respiratory or internal mucosal surfaces, very little was known about how antiviral immune responses are developed and regulated in the oral cavity.
“A significant number of viral pathogens either directly infect oral epithelial cells or have a transient presence in the oral cavity owing to infection and release from other tissues. This piqued our interest and we investigated how antiviral immunity is regulated and manipulated in the oral cavity,” Dr Bagaitkar commented.
Gingivalis and interferon production and activation
In the study, the researchers used human gingival tissues, mouse models and in vitro approaches to show that the production of interferons, which are important antiviral cytokines that play a critical role in limiting viral infection, and antiviral immunity are severely compromised in the presence of the oral bacterial pathogen Porphyromonas gingivalis.
“The most interesting aspect of our study is that we found how bacterial residents of the oral biofilm can determine the efficacy of host interferon responses,” Dr Bagaitkar explained and added that the finding is rather innovative and has important implications for understanding what might predispose an individual to a viral infection.
She further commented: “Specifically, we identified P. gingivalis, a periodontal pathogen and a master manipulator of host immune responses, as able to entirely shut down interferon responses by attacking three separate arms of the interferon response pathway. We found that mice and human periodontitis patients who are chronically infected with P. gingivalis have an intrinsically lowered ability to produce interferons and activate interferon-stimulated genes in response to viral pathogenic stimuli. Furthermore, we found that P. gingivalis-derived proteases cleave interferon receptors, making cells refractory to exogenous sources of interferons, either produced by other cells or injected.”
“We found how bacterial residents of the oral biofilm can determine the efficacy of host interferon responses”
— Dr Juhi Bagaitkar, University of Louisville
P. gingivalis has previously been associated with numerous other chronic and degenerative diseases, including Alzheimer’s disease and rheumatoid arthritis. Additionally, recent studies have reported that immune suppression in patients having periodontitis can enhance their susceptibility to a viral infection. The present study has consolidated the previous findings.
“Our studies now add to this body of literature by showing that periodontitis, a bacterial infection-driven chronic inflammatory and tissue destructive disease, might enhance the oral viral burden,” Dr Bagaitkar said and added that some of the viruses that affect the oral cavity include herpes, HIV, human papillomavirus and also SARS-CoV-2.
In light of the findings, the researchers commented that future studies will focus on investigating the development of strategies to bolster oral antiviral immunity against viruses that infect oral tissues.
The study, titled “Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa”, was published online on 21 December 2021 in Proceedings of the National Academy of Sciences of the United States of America.
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