PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications

Abstract

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.

Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses

“…Secondly, very low MOIs such as this do not stimulate early cytokine responses ex vivo because they are often rapidly cleared. Thirdly, there is now good evidence that PAMPs and DAMPs may not only be associated with live bacteria but also in soluble forms not associated with bacteria [60,61]. Fourth, viable bacteria are counted in cfu/mL, but many studies also quantify genome copies/mL using nucleic acid amplification techniques [62].…”

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators

“…TLRs, the main exponents of the PPR (Pattern Recognition Receptor) family, detect pathogens and damaged cells through pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). They are expressed on immune cells and their activation results in the secretion of pro-inflammatory cytokines (including IL-1, IL-6, IL-8, TNF, IL-33, and IFN-γ) [ 64 , 65 ] and in the regulation of the balance between Th1 and Th2 immune responses [ 66 ]. Beside their pro-inflammatory role, some studies have suggested that TLR2 and TLR4 are also involved in EMT through the modulation of the TGF-β pathway [ 67 ].…”

Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation

“…In the extracellular environment, ATP functions as one of the damage-associated molecular patterns (DAMPs), in which elevated concentration leads to the activation of immune system cells and the production of pro-inflammatory cytokines and factors [ 185 ]. Also, ATP stimulation of MSCs results in the secretion of various enzymes and factors, including COX-2, IDO, and iNOS, which stimulate the pro-inflammatory activity of the immune system [ 186 , 187 ].…”