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Danger signals - damaged-self recognition across the tree of life.

Heil M, Land WG - Front Plant Sci (2014)

Bottom Line: Danger signals are "damage-associated molecular patterns" (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells.Ca(2+)-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life.Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Ingeniería Genética, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional-Irapuato Irapuato, México.

ABSTRACT
Multicellular organisms suffer injury and serve as hosts for microorganisms. Therefore, they require mechanisms to detect injury and to distinguish the self from the non-self and the harmless non-self (microbial mutualists and commensals) from the detrimental non-self (pathogens). Danger signals are "damage-associated molecular patterns" (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells. Seemingly ubiquitous DAMPs are extracellular ATP or extracellular DNA, fragmented cell walls or extracellular matrices, and many other types of delocalized molecules and fragments of macromolecules that are released when pre-existing precursors come into contact with enzymes from which they are separated in the intact cell. Any kind of these DAMPs enable damaged-self recognition, inform the host on tissue disruption, initiate processes aimed at restoring homeostasis, such as sealing the wound, and prepare the adjacent tissues for the perception of invaders. In mammals, antigen-processing and -presenting cells such as dendritic cells mature to immunostimulatory cells after the perception of DAMPs, prime naïve T-cells and elicit a specific adaptive T-/B-cell immune response. We discuss molecules that serve as DAMPs in multiple organisms and their perception by pattern recognition receptors (PRRs). Ca(2+)-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life. Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.

No MeSH data available.


Related in: MedlinePlus

MAPKs in the DAMP perception in innate immune cells. DAMPs interact with multiple PRRs of innate immune cells and trigger the maturation of DC to mature APCs or the synthesis and release of Type I interferons (IFNs), cytokines, chemokines, and other pro-inflammatory compounds. Toll-like receptors (TLRs) such as TLR2 or TLR4 are located on the outer membrane, sense class I DAMPs (such as HMGB1) and initiate a pathway dependent on MyD88 and other mediators that triggers cascades that depend on mitogen-activated protein kinases, MAPKs (among others) and activate NF-κB and other transcription factors (TF). Nucleic acids can also be sensed via TLRs 3,7,8,9, which are located on the endosomal membrane, and activate the same downstream pathways.
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Figure 3: MAPKs in the DAMP perception in innate immune cells. DAMPs interact with multiple PRRs of innate immune cells and trigger the maturation of DC to mature APCs or the synthesis and release of Type I interferons (IFNs), cytokines, chemokines, and other pro-inflammatory compounds. Toll-like receptors (TLRs) such as TLR2 or TLR4 are located on the outer membrane, sense class I DAMPs (such as HMGB1) and initiate a pathway dependent on MyD88 and other mediators that triggers cascades that depend on mitogen-activated protein kinases, MAPKs (among others) and activate NF-κB and other transcription factors (TF). Nucleic acids can also be sensed via TLRs 3,7,8,9, which are located on the endosomal membrane, and activate the same downstream pathways.

Mentions: We suggest to divide mammalian DAMPs into five classes (Table 1) because they are sensed by distinct members of five families of PRRs: TLRs (Kawai and Akira, 2010), receptor for advanced glycation endproducts (RAGE; Lee and Park, 2013), NOD-like receptors (NLRs; Zhong et al., 2013), RIG-I-like receptors (RLRs; Wu and Chen, 2014), and AIM2-like receptors (ALRs; Wu and Chen, 2014). Class I DAMPs comprise, for example, the important chromatin, high-mobility group protein B1 (HMGB1; Kang et al., 2014; Tsung et al., 2014), or heat shock proteins (HSPs; Seigneuric et al., 2011; Tamura et al., 2012), which are perceived via specific membrane-bound TLRs that act as PRRs and activate MAPK signaling cascades to induce inflammatory cytokines (Figure 3). MAPK signaling cascades are highly conserved elements in all eukaryotic cells that trigger the responses to multiple developmental or environmental stimuli. MAPK signaling cascades consist of three layers of kinases, in which MAPKs are activated via the simultaneous phosphorylation of a tyrosine residue and a threonine residue that are localized in an evolutionarily conserved “Thr-X-Tyr” motif in the activation loop of the MAPK. This phosphorylation is catalyzed by MAPK kinases (MAPPKs) that exhibit specificity both toward their MAPK and their respective upstream MAPKK kinase (MAPKKK). The latter type of enzymes forms a very diverse group of protein kinases that activate MAPKKs by serine/threonine phosphorylation, again in a conserved motif. Among others, MAPK cascades are involved in the perception of diverse DAMPs and PAMPs and, thus, represent central elements in the immune response to damage or infection (Kyriakis and Avruch, 2012).


Danger signals - damaged-self recognition across the tree of life.

Heil M, Land WG - Front Plant Sci (2014)

MAPKs in the DAMP perception in innate immune cells. DAMPs interact with multiple PRRs of innate immune cells and trigger the maturation of DC to mature APCs or the synthesis and release of Type I interferons (IFNs), cytokines, chemokines, and other pro-inflammatory compounds. Toll-like receptors (TLRs) such as TLR2 or TLR4 are located on the outer membrane, sense class I DAMPs (such as HMGB1) and initiate a pathway dependent on MyD88 and other mediators that triggers cascades that depend on mitogen-activated protein kinases, MAPKs (among others) and activate NF-κB and other transcription factors (TF). Nucleic acids can also be sensed via TLRs 3,7,8,9, which are located on the endosomal membrane, and activate the same downstream pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215617&req=5

Figure 3: MAPKs in the DAMP perception in innate immune cells. DAMPs interact with multiple PRRs of innate immune cells and trigger the maturation of DC to mature APCs or the synthesis and release of Type I interferons (IFNs), cytokines, chemokines, and other pro-inflammatory compounds. Toll-like receptors (TLRs) such as TLR2 or TLR4 are located on the outer membrane, sense class I DAMPs (such as HMGB1) and initiate a pathway dependent on MyD88 and other mediators that triggers cascades that depend on mitogen-activated protein kinases, MAPKs (among others) and activate NF-κB and other transcription factors (TF). Nucleic acids can also be sensed via TLRs 3,7,8,9, which are located on the endosomal membrane, and activate the same downstream pathways.
Mentions: We suggest to divide mammalian DAMPs into five classes (Table 1) because they are sensed by distinct members of five families of PRRs: TLRs (Kawai and Akira, 2010), receptor for advanced glycation endproducts (RAGE; Lee and Park, 2013), NOD-like receptors (NLRs; Zhong et al., 2013), RIG-I-like receptors (RLRs; Wu and Chen, 2014), and AIM2-like receptors (ALRs; Wu and Chen, 2014). Class I DAMPs comprise, for example, the important chromatin, high-mobility group protein B1 (HMGB1; Kang et al., 2014; Tsung et al., 2014), or heat shock proteins (HSPs; Seigneuric et al., 2011; Tamura et al., 2012), which are perceived via specific membrane-bound TLRs that act as PRRs and activate MAPK signaling cascades to induce inflammatory cytokines (Figure 3). MAPK signaling cascades are highly conserved elements in all eukaryotic cells that trigger the responses to multiple developmental or environmental stimuli. MAPK signaling cascades consist of three layers of kinases, in which MAPKs are activated via the simultaneous phosphorylation of a tyrosine residue and a threonine residue that are localized in an evolutionarily conserved “Thr-X-Tyr” motif in the activation loop of the MAPK. This phosphorylation is catalyzed by MAPK kinases (MAPPKs) that exhibit specificity both toward their MAPK and their respective upstream MAPKK kinase (MAPKKK). The latter type of enzymes forms a very diverse group of protein kinases that activate MAPKKs by serine/threonine phosphorylation, again in a conserved motif. Among others, MAPK cascades are involved in the perception of diverse DAMPs and PAMPs and, thus, represent central elements in the immune response to damage or infection (Kyriakis and Avruch, 2012).

Bottom Line: Danger signals are "damage-associated molecular patterns" (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells.Ca(2+)-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life.Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Ingeniería Genética, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional-Irapuato Irapuato, México.

ABSTRACT
Multicellular organisms suffer injury and serve as hosts for microorganisms. Therefore, they require mechanisms to detect injury and to distinguish the self from the non-self and the harmless non-self (microbial mutualists and commensals) from the detrimental non-self (pathogens). Danger signals are "damage-associated molecular patterns" (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells. Seemingly ubiquitous DAMPs are extracellular ATP or extracellular DNA, fragmented cell walls or extracellular matrices, and many other types of delocalized molecules and fragments of macromolecules that are released when pre-existing precursors come into contact with enzymes from which they are separated in the intact cell. Any kind of these DAMPs enable damaged-self recognition, inform the host on tissue disruption, initiate processes aimed at restoring homeostasis, such as sealing the wound, and prepare the adjacent tissues for the perception of invaders. In mammals, antigen-processing and -presenting cells such as dendritic cells mature to immunostimulatory cells after the perception of DAMPs, prime naïve T-cells and elicit a specific adaptive T-/B-cell immune response. We discuss molecules that serve as DAMPs in multiple organisms and their perception by pattern recognition receptors (PRRs). Ca(2+)-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life. Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.

No MeSH data available.


Related in: MedlinePlus