Assembly and localization of Toll-like receptor signalling complexes

Symmons, Martyn F.; Gangloff, Monique; Bryant, Clare E.

doi:10.1038/nri3713

Cited by 716 publications

(671 citation statements)

References 112 publications

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“…S3E). Whether such a structure actually occurs remains to be determined, but in animals TIR domains are known to oligomerize and heterodimerize to transmit signals (44). Analogous to this hypothetical RBA1 oligomer, the animal TIR protein MyD88 is proposed to form a helical homo-oligomer (with multiple, distinct interaction surfaces) as part of a larger complex of TIR-containing proteins (45).…”

Section: Discussionmentioning

confidence: 99%

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death inArabidopsis

Nishimura

Anderson

Cherkis

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

131

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Detection of pathogens by plants is mediated by intracellular nucleotide-binding site leucine-rich repeat (NLR) receptor proteins. NLR proteins are defined by their stereotypical multidomain structure: an N-terminal Toll-interleukin receptor (TIR) or coiled-coil (CC) domain, a central nucleotide-binding (NB) domain, and a C-terminal leucine-rich repeat (LRR). The plant innate immune system contains a limited NLR repertoire that functions to recognize all potential pathogens. We isolated Response to the bacterial type III effector protein HopBA1 (RBA1), a gene that encodes a TIR-only protein lacking all other canonical NLR domains. RBA1 is sufficient to trigger cell death in response to HopBA1. We generated a crystal structure for HopBA1 and found that it has similarity to a class of proteins that includes esterases, the hemebinding protein ChaN, and an uncharacterized domain of Pasteurella multocida toxin. Self-association, coimmunoprecipitation with HopBA1, and function of RBA1 require two previously identified TIR-TIR dimerization interfaces. Although previously described as distinct in other TIR proteins, in RBA1 neither of these interfaces is sufficient when the other is disrupted. These data suggest that oligomerization of RBA1 is required for function. Our identification of RBA1 demonstrates that "truncated" NLRs can function as pathogen sensors, expanding our understanding of both receptor architecture and the mechanism of activation in the plant immune system. plant immunity | NLR | Toll-interleukin-1 receptor homology domain | oligomerization | type III secretion

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Section: Discussionmentioning

confidence: 99%

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death inArabidopsis

Nishimura

Anderson

Cherkis

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

131

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“…An explanation for this effect may partly derive from alterations in dopaminergic transmission; similar to the result obtained using ibudilast, (+)-naloxone suppresses morphine-induced dopamine release into the NAc as measured by in vivo microdialysis . Opioid-induced TLR-mediated signaling appears to depend on microglial p38 MAPK (Zhang et al, 2012), a pathway associated with cAMP-responsive element-binding protein (CREB) -mediated transcription of pro-inflammatory cytokines and chemokines (Gay et al, 2014). Thus, in addition to opioid receptor-mediated effects on neurons, TLR signaling can strongly influence conditioning to the motivational properties of different classes of abused opioid drugs.…”

Section: Opioids Glia and Neuroimmune Signalingmentioning

confidence: 99%

“…These so called 'on' and 'off' signals that regulate microglial responses are extremely varied and beyond the scope of this review (see Biber et al, 2007). We focus in the sections that follow on the signaling pathways associated with Toll-like receptor (TLR) complexes, as these are the most extensively characterized receptors for host defense, as well as in the response to drugs of abuse (Gay et al, 2014;Trotta et al, 2014). See Box 1 BOX 1 Toll-like Receptors: Recognition, Signaling, and Cell Types Toll-like receptors (TLRs) are transmembrane pattern recognition receptors (PRRs) that have an essential role in coordinating innate immune responses through detection of microbial pathogens (Kawai and Akira, 2006).…”

Section: Microgliamentioning

confidence: 99%

“…See Box 1 BOX 1 Toll-like Receptors: Recognition, Signaling, and Cell Types Toll-like receptors (TLRs) are transmembrane pattern recognition receptors (PRRs) that have an essential role in coordinating innate immune responses through detection of microbial pathogens (Kawai and Akira, 2006). All TLRs contain a cytosolic Toll/interleukin-1 receptor (TIR) domain and a leucine-rich ectodomain that accommodates binding of highly conserved pathogen-associated molecular patterns (PAMPs), such as bacterial lipoproteins, bacterial flagellin, and viral single-stranded RNA (Gay et al, 2014;Kawai and Akira, 2006). Beyond pathogen recognition, there is increasing evidence that TLRs may also recognize danger-associated molecular patterns (DAMPs), which include numerous endogenous ligands such as peptides, lipoproteins, glycosaminoglycans, and nucleic acids released by activated or necrotic cells (reviewed in Piccinini and Midwood, 2010).…”

Section: Microgliamentioning

confidence: 99%

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Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

223

170

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Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

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“…4 Immune activation and a massive release of proinflammatory mediators are hallmarks of ALI and ARDS, 5 and mechanical ventilation may further exacerbate the inflammatory response. [6][7][8] Cytokines recruit effector cells, which amplify the inflammatory response.…”

mentioning

confidence: 99%

Sevoflurane Abolishes Oxygenation Impairment in a Long-term Rat Model of Acute Lung Injury

Kellner

Müller

Piegeler

et al. 2017

Survey of Anesthesiology

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BACKGROUND Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI. METHODS Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin , IL-12/12a, transforming growth factor-, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation. RESULTS After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups. CONCLUSIONS Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI. A cute lung injury (ALI) frequently requires both mechanical ventilation and sedation in the intensive care unit (ICU). 1,2 Currently, approximately 10% of patients treated in the ICU experience ALI or acute respiratory distress syndrome (ARDS), 3 and mortality rates of up to 50% have been described. 4 Immune activation and a massive release of proinflammatory mediators are hallmarks of ALI and ARDS, 5 and mechanical ventilation may further exacerbate the inflammatory response. 6-8 Cytokines recruit effector cells, which amplify the inflammatory response. 9 Bacterial lipopolysaccharides (LPSs) are complex glycolipids found on the outer membrane of Gr...

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Assembly and localization of Toll-like receptor signalling complexes

Cited by 716 publications

References 112 publications

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death inArabidopsis

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death inArabidopsis

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Sevoflurane Abolishes Oxygenation Impairment in a Long-term Rat Model of Acute Lung Injury

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