TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1β and caspase-1 in monocytes and dendritic cells

Phagosomal signaling byBorrelia burgdorferiin human monocytes involves Toll-like receptor (TLR) 2 and TLR8 cooperativity and TLR8-mediated induction of IFN-β

“…1A, we then showed that inhibition of TLR8 by IRS957 eliminated transcription of IFN-β, whereas induction of this cytokine by the spirochete was unaffected by blocking TLR7 with IRS661 (P = 0.17 vs. no inhibitor) or TLR9 with IRS869 (P = 0.27 vs. no inhibitor). The specificity of IRS957 for TLR8 in human monocytes has been previously confirmed by exclusion of reactivity to TLR7 and TLR9 (32). Herein, we confirmed the specific inhibitory effect of IRS957 by demonstrating that production of IFN-β was markedly decreased in response to the TLR7/8 agonist R848 (Fig.…”

“…Having established that TLR2 signaling alone cannot explain the type I IFN responses to live Bb, we hypothesized that activation of an endosomal TLR could be responsible for the induction of IFN-β in the monocyte. To explore this possibility, we took advantage of the availability of specific inhibitory DNA-oligonucleotide sequences (IRSs) that have the ability to block ligation of TLR7, TLR8, or TLR9 (31,32). These inhibitors were recently used by Petzke et al (22) to demonstrate that induction of IFN-α in Bb-infected pDCs is dependent on TLR7 and TLR9.…”

DAMPs as mediators of sterile inflammation in aging-related pathologies

“…MAMPs DAMPs 2 Extracellular Lipopeptide (Takeda et al, 2002) Biglycan (Schaefer et al, 2005), HMGB1 (Yu et al, 2006), HSP60 (Zanin-Zhorov et al, 2003), HSP70 (Vabulas et al, 2002a), human cadiac myosin (Zhang et al, 2009), LMW-HA (Scheibner et al, 2006), MSU crystals (Liu-Bryan et al, 2005), Gp96 (Warger et al, 2006), H␤D-3 (Guo et al, 2013), SPA (Montalbano et al, 2013;Murakami et al, 2002), SPD (Montalbano et al, 2013), EDN , APLAs (Satta et al, 2011), SAA (Cheng et al, 2008) and Versican (Wang et al, 2009) 4 Lipopolysaccharide (Lu et al, 2008) Biglycan (Schaefer et al, 2005), BD-2 (Biragyn et al, 2002;Vora et al, 2004), fibrinogen (Hodgkinson et al, 2008), fibronectin (Okamura et al, 2001), Imidazoquinoline (Colak et al, 2014) and viral ssRNA (Colak et al, 2014;Diebold et al, 2004) ssRNA (Diebold et al, 2004), siRNA (Robbins et al, 2009) and APLAs (Hurst et al, 2009), TLR8 can recognize human cardiac myosin (Zhang et al, 2009) 9 Unmethylated CpG dinucleotides (Takeshita et al, 2001) IgG chromatin complexes (Boulé et al, 2004), DNA (Rutz et al, 2004) and HMGB1 (Ivanov et al, 2007) as receptors for yet-to-be discovered DAMPs. In addition, DAMPs such as HMGB1 exhibit the potential to interact with multiple TLRs in different cells (Apetoh et al, 2007;Tang et al, 2007a;Tian et al, 2007).…”

New Insights into the Biology and Pathobiology of Beta2-Glycoprotein I

“…In addition, costimulation of these cells with a dual TLR7 and TLR8 agonist in the presence of the autoantibody further increased mRNA expression and secretion of IL-1β [46]. Overexpression of TLR8 and increased production of tumor necrosis factor-α in peripheral blood monocytes stimulated with this autoantibody also have been reported.…”

“…An antibody from a patient with APS upregulated TLR7 and TLR8 expression in plasmacytoid dendritic cells and monocytes, respectively [46]. In addition, costimulation of these cells with a dual TLR7 and TLR8 agonist in the presence of the autoantibody further increased mRNA expression and secretion of IL-1β [46].…”