Recognition of damage-associated molecular patterns related to nucleic acids during inflammation and vaccination

Abstract

All mammalian cells are equipped with large numbers of sensors for protection from various sorts of invaders, who, in turn, are equipped with molecules containing pathogen-associated molecular patterns (PAMPs). Once these sensors recognize non-self antigens containing PAMPs, various physiological responses including inflammation are induced to eliminate the pathogens. However, the host sometimes suffers from chronic infection or continuous injuries, resulting in production of self-molecules containing damage-associated molecular patterns (DAMPs). DAMPs are also responsible for the elimination of pathogens, but promiscuous recognition of DAMPs through sensors against PAMPs has been reported. Accumulation of DAMPs leads to massive inflammation and continuous production of DAMPs; that is, a vicious circle leading to the development of autoimmune disease. From a vaccinological point of view, the accurate recognition of both PAMPs and DAMPs is important for vaccine immunogenicity, because vaccine adjuvants are composed of several PAMPs and/or DAMPs, which are also associated with severe adverse events after vaccination. Here, we review as the roles of PAMPs and DAMPs upon infection with pathogens or inflammation, and the sensors responsible for recognizing them, as well as their relationship with the development of autoimmune disease or the immunogenicity of vaccines.

The role of P2X7 receptors in tissue fibrosis: a brief review

“…When cells are attacked by exogenous pathogens, host cellular receptors recognize pathogen-associated molecular patterns (PAMPs), small molecular motifs conserved among microbes. In many cases, pathogen elimination requires the damage-associated molecular patterns (DAMPs) that include endogenous intracellular molecules released by activated or necrotic cells [37]. PAMPs such as lipopolysaccharide (LPS) can induce the synthesis of pro-inflammatory cytokines such as pro-interleukin (IL)-1β [38], and its release occurs after NALP-3 inflammasome complex activation [39].…”

Pullulan-histone antibody nanoconjugates for the removal of chromatin fragments from systemic circulation

“…Histones, nucleic acids, HMBG1 (non-histone DNA binding protein from chromatin) etc belong to the class of DAMPs (Damageassociated molecular pattern molecules). DAMPs are associated with inflammatory response in non-infectious immune response [47,48]. It is reported that the DAMPs leads to massive inflammatory reaction and also promotes further production of DAMPs, thus a cyclic reaction [47].…”

“…DAMPs are associated with inflammatory response in non-infectious immune response [47,48]. It is reported that the DAMPs leads to massive inflammatory reaction and also promotes further production of DAMPs, thus a cyclic reaction [47]. Histones and non-degraded DNA accumulated in macrophages leads to the production of high levels of type 1 interferons (IFN) [49].…”

Danger in the Intensive Care Unit

“…Moreover, the endosymbiotic theory suggests that mitochondria originate from freeliving bacteria, and as such, mitochondria have their own DNA (mtDNA). Nuclear DNA (nDNA), RNA, and mtDNA can bind to TLRs and as such stimulate the production of proinflammatory cytokines (55,56).…”