Role of Porphyromonas gingivalis in the downregulation of NLRp3 inflammasome in periodontitis

Abstract

The innate immune response is the body's first line of defense against pathogens. The innate immune system recognizes pathogens, including bacteria and viruses by engagement of the germline-encoded pattern recognition receptors (PRRs). There are five families of PRRs which are able to sense vast families of microbial components, referred to as pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs), they are host cell components produced during inflammation or environmentally derived. Although PRRs are predominately expressed by innate immune cells, many of the PRRs are also found on other cells including epithelial, endothelial, and cells of the adaptive immune system. PRR engagement by its ligand induces downstream signaling cascades that induce multiple effects, including activation of innate immune cells and cytokine/chemokine production for the recruitment of immune cells to the site of infection or tissue damage. There are multiple inflammasomes that are formed, which are named for their sensor PRR that induces its activation. It is still not clear how many sensors are capable of forming inflammasomes, with strong literature support for over 10 different inflammasomes, including NLRP1, NLRP3, NLRP6, NLRP12, pyrin, NAIP/NLRC4, RIG-I AIM2, IFI16, NLRC3, and NLP6 5,7 which are recently reviewed. The study of periodontal disease thus represents an excellent model to study the role of inflammasomes due to the abundance of Microbe Associated Molecular Patterns (MAMP) and DAMPs and the elevated proportion of macrophages in the tissue microenvironment.