TLR8 and NOD signaling synergistically induce the production of IL-1β and IL-23 in monocyte-derived DCs and enhance the expression of the feedback inhibitor SOCS2

Schwarz, Harald; Posselt, Gernot; Wurm, Philipp; Ulbing, Matthias; Duschl, Albert; Horejs‐Hoeck, Jutta

doi:10.1016/j.imbio.2012.06.007

Cited by 40 publications

(22 citation statements)

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“…Furthermore, we demonstrated that activation by L lactis G121 RNA can be substantially increased by NOD2 activation, a synergistic response of TLR8 and NOD2 that has also been shown elsewhere. 46,47 Therefore the apparent difference in the amount of IL-12 induced by whole bacteria versus RNA might be explained by the fact that the degree of activation after the uptake and processing of whole bacteria is much stronger because of synergistic activation processes.…”

Section: Discussionmentioning

confidence: 99%

Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects

Stein

Brand²,

Jenckel

et al. 2017

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects

Stein

Brand²,

Jenckel

et al. 2017

Journal of Allergy and Clinical Immunology

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“…Even if the LPS impurities alone do not affect those cells, it has to be considered that low LPS concentrations together with other types of stimuli (e.g. cytokines or NOD-like receptor ligands) could have synergistic effects [25] – [27] and thus produce erroneous data. To avoid endotoxin contamination that may compromise research experiments, we recommend working with proteins that have been expressed under largely endotoxin-free conditions.…”

Section: Discussionmentioning

confidence: 99%

Residual Endotoxin Contaminations in Recombinant Proteins Are Sufficient to Activate Human CD1c+ Dendritic Cells

et al. 2014

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Many commercially available recombinant proteins are produced in Escherichia coli, and most suppliers guarantee contamination levels of less than 1 endotoxin unit (EU). When we analysed commercially available proteins for their endotoxin content, we found contamination levels in the same range as generally stated in the data sheets, but also some that were higher. To analyse whether these low levels of contamination have an effect on immune cells, we stimulated the monocytic cell line THP-1, primary human monocytes, in vitro differentiated human monocyte-derived dendritic cells, and primary human CD1c+ dendritic cells (DCs) with very low concentrations of lipopolysaccharide (LPS; ranging from 0.002–2 ng/ml). We show that CD1c+ DCs especially can be activated by minimal amounts of LPS, equivalent to the levels of endotoxin contamination we detected in some commercially available proteins. Notably, the enhanced endotoxin sensitivity of CD1c+ DCs was closely correlated with high CD14 expression levels observed in CD1c+ DCs that had been maintained in cell culture medium for 24 hours. When working with cells that are particularly sensitive to LPS, even low endotoxin contamination may generate erroneous data. We therefore recommend that recombinant proteins be thoroughly screened for endotoxin contamination using the limulus amebocyte lysate test, fluorescence-based assays, or a luciferase based NF-κB reporter assay involving highly LPS-sensitive cells overexpressing TLR4, MD-2 and CD14.

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“…In a more recent work, it was shown that NOD1 and TLR2 cooperate to enhance human CD8 T cells proliferation and expansion, and this cooperating action caused an enhanced secretion of IL-2, IFN- γ , and TNF- α that was related to increased activation of NF- κ B, JNK, and p38 signaling pathways [ 177 ]. Simultaneous stimulation of monocytes-derived DC with NOD1 and NOD2 ligands combined with TLR7/8 or TLR4 agonists results in highly increased production of IL-1 β and IL-23 and expression of the inhibitor suppressor of cytokine signaling 2 (SOCS2), where the NOD1/TLR agonists combination was more relevant for the synergistic activity observed [ 178 ]. Altogether, these results clarify the existence of a cooperative action of TLRs and NLRs, which become relevant in the context of infection by bacteria that can be recognized by extra- and intracytosolic receptors.…”

Section: Combined Response Of Tlrs and Nlrs Signalingmentioning

confidence: 99%

Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria

Oviedo-Boyso

Bravo-Patiño

Baizabal-Aguirre

2014

Mediators of Inflammation

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Early sensing of pathogenic bacteria by the host immune system is important to develop effective mechanisms to kill the invader. Microbial recognition, activation of signaling pathways, and effector mechanisms are sequential events that must be highly controlled to successfully eliminate the pathogen. Host recognizes pathogens through pattern-recognition receptors (PRRs) that sense pathogen-associated molecular patterns (PAMPs). Some of these PRRs include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene-I- (RIG-I-) like receptors (RLRs), and C-type lectin receptors (CLRs). TLRs and NLRs are PRRs that play a key role in recognition of extracellular and intracellular bacteria and control the inflammatory response. The activation of TLRs and NLRs by their respective ligands activates downstream signaling pathways that converge on activation of transcription factors, such as nuclear factor-kappaB (NF-κB), activator protein-1 (AP-1) or interferon regulatory factors (IRFs), leading to expression of inflammatory cytokines and antimicrobial molecules. The goal of this review is to discuss how the TLRs and NRLs signaling pathways collaborate in a cooperative or synergistic manner to counteract the infectious agents. A deep knowledge of the biochemical events initiated by each of these receptors will undoubtedly have a high impact in the design of more effective strategies to control inflammation.

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TLR8 and NOD signaling synergistically induce the production of IL-1β and IL-23 in monocyte-derived DCs and enhance the expression of the feedback inhibitor SOCS2

Cited by 40 publications

References 50 publications

Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects

Endosomal recognition of Lactococcus lactis G121 and its RNA by dendritic cells is key to its allergy-protective effects

Residual Endotoxin Contaminations in Recombinant Proteins Are Sufficient to Activate Human CD1c+ Dendritic Cells

Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria

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