TABLE 1.

Summary of key Danger Associated Molecular Patterns, their receptors and mechanisms.

Origin	DAMP	Receptor	Function (standard font = pro-inflammatory; italics = anti-inflammatory)	References
Extracellular Matrix	Aggrecan 32 mer fragment	TLR2	(iNOS), CCL2, IL-1α, IL-6, MMP12 MMP13 and ADAMTS5	Stevens et al., 2008
	Biglycan	TLR2/4	Increases levels of reactive oxygen species, CXCL-1, CCL2 and HSP70, and activates NLRP3 inflammasome by Caspase-1 and the maturation of IL-1β Activating a TLR co-adaptor that activates IFN1 signaling	Frey et al., 2013; Schaefer, 2014; Roedig et al., 2019
	Decorin	TLR2/4	Decreases TGFβ1 and IL-10 and increases levels of apoptosis	Merline et al., 2011
	*Fibronectin	TLR2/4	Promotes pro-inflammatory mediators and phagocytosis by macrophages	Haruta et al., 2013; Fei et al., 2018
	Fibrinogen	TLR4	Activation of monocytes	Al-Ofi et al., 2014
	LMW-HA	TLR2/4	Activates NLRP3 inflammasome by Caspase-1 and the maturation of IL-1β. Activates NF-kB	Merline et al., 2011
	HMW-HA	TLR2	Activates a TLR co-adaptor that activates IFN1 signaling	Scheibner et al., 2006; Frey et al., 2013
	Heparin sulfate	TLR4, RAGE	Activation of NF-kB	Xu et al., 2011
	Tenascin C	TLR4	Synthesis of pro-inflammatory cytokines	Midwood et al., 2009
	Versican	TLR2/4 CD14	IL-6, IL-1β, Il-12 and CCL2 production Increasing IL-6 (anti-inflammatory pathways), IL-10	Wight et al., 2014
Cytosolic	ATP	P2XR P2YR	Attracts macrophages by inflammasome activation MAPK wound healing response	Venereau et al., 2015
	Cyclophilin	CD 147	Chemotaxis and the production of pro-inflammatory factors	Burkrinsky, 2014
	F-actin	DNGR1	DNGR1 recognizes the released F-actin, which causes the uptake of damaged or dead cells	Brown, 2012
	Heat Shock Protein	TLR2/4	MyD88 dependent activation of NF-kB	Tolle and Standiford, 2013; Relja et al., 2018
	S100 proteins	TLR4, CD147 RAGE	Leads to apoptosis and activates ERK and NF-kB or AP1	Ghavami et al., 2010; Xia et al., 2018
	*Soluble amyloid beta	TLR2/4	Enhanced TNF driven inflammation	Wang et al., 2019
	Uric Acid	NLRP3	Inflammasome activation and induction of IL-1β maturation	Braga et al., 2017
Mitochondrial	mtDNA	TLR9	p38 MAPK and NF-kB activation	Zhang et al., 2010; Zhang et al., 2014; Magna and Pisetsky, 2016; Bao et al., 2016
Nuclear	*Cell free DNA	TLR9	Activation of NF-kB and AP1	Magna and Pisetsky, 2016
	Circulating Histones	TLR9	Inflammation through the activation of NF-kB	Huang et al., 2011; Kawai et al., 2016
	Extracellular self RNA	TLR7 TLR3	Sensitizes other TLR working synergistically with their other ligands MAPK, NF-κB, and IRF-5/7 pathways through MyD88 signaling	Karikó et al., 2004; Cavassani et al., 2008; Thompson et al., 2011; Noll et al., 2017; Petes et al., 2017
	*HMGB1	TLR2 TLR4 TLR9	Activation of NF-kB, and MAPK signaling though ERK and p38, release of MMPs	Qin et al., 2006; Nie et al., 2016
				Menon et al., 2011; Bredeson et al., 2014; Plazyo et al., 2016
	IL-1α	IL-1R	MAPK signaling and NF-kB activation	Betheloot and Latz, 2017
	IL-33	ST2	NF-kB activation and TNF production	Isnadi et al., 2018
	SAP130	Mincle	Triggering pro-inflammatory cytokine secretion	Zhou et al., 2016; Patkin et al., 2017

* denotes has been studied in the fetal membranes or cells of the fetal membranes. ADAMTS5, ADAM metallopeptidase with Thrombospondin type 1 motif 5; AP-1, Activator protein 1; CD, Cluster Differentiation; DNGR1, Dendritic cell natural killer lectin group receptor-1; ERK, extracellular-signal-regulated kinase; HSP, Heat Shock protein; IFN1, Interferon; IL, Interleukin; iNOS, Inducible Nitric Oxide; IRF, Interferon regulatory factors; MMP, Matrix Metalloproteinase; MyD88, myeloid differentiation primary response protein 88; NF-kB, Nuclear Factor Kappa B; NLRP3, LRR- and pyrin domain-containing protein 3; RAGE, advanced glycation end products; ST2, suppression of tumorigenicity 2; TGF, Transforming growth factor; TLR, Toll-like receptor; TNF, Tumor Necrosis Factor.