Oral infections, NETosis and autoimmunity. Periodontitis is a common infection and is seen in 47% of the US adult population. It is an inflammation of the soft and hard tissues supporting the tooth, and it is initiated by the accumulation of dental plaque or biofilm between the tooth and the gingival epithelium. Bacteria and their products invade the gingival epithelium and stimulate inflammation, leading to progressive damage of the local tissues, bone resorption, and tooth loss. The long term goal of this project is to investigate the mechanisms involved in the initiation and amplification of autoimmune responses by oral infections with periodontogenic bacteria.
Currently we are investigating how Aggregatibacter actinomycetemcomitans (Aa), a gram negative periodontogenic bacterium, influences the pathogenesis of systemic lupus erythematosus (SLE) in humans and mice. SLE is a chronic autoimmune disease affecting 1.5 million Americans. It targets multiple organ systems including kidney, joints, lungs, heart, brain and skin. SLE patients show dysregulated adaptive and innate immunity characterized by the presence of antibodies to nuclear and cytoplasmic auto-antigens and elevated type I IFN.
Our current hypothesis is that Aa induces the formation of neutrophil extracellular traps (NETs), a pro-inflammatory form of cell death associated with the extrusion of chromatin strands that are decorated with bactericidal peptides and enzymes. The extracellular histones and nucleosomes released from the dying cells are potent inducers of innate immunity. In SLE, they may also serve as a source of autoantigens. Thus, in this project we are investigating the mechanisms involved in Aa mediated amplification of autoimmunity in lupus-prone NZM2328 mice. In addition, we are also exploring how changes in oral microbiome influences the progression of autoimmune disorders.
This project integrating infection, mucosal immunology and autoimmunity is expected to increase the awareness for improving oral health in lupus patients and the general population.