Rabbit Anti-Human IRF5 (a.a. 401-498) Polyclonal antibody

TLR8 is the major endosomal sensor of degraded RNA in human monocytes and macrophages. It has been implicated in the sensing of viruses and more recently also bacteria. We previously identified a TLR8-IFN regulatory factor 5 (IRF5) signaling pathway that mediates IFN beta and interleukin-12 (IL-12) induction by Staphylococcus aureus and is antagonized by TLR2. The relative importance of TLR8 for the sensing of various bacterial species is however still unclear. We here compared the role of TLR8 and IRF5 for the sensing of Group B Streptococcus (GBS), S. aureus, and Escherichia coli in human primary monocytes and monocyte-derived macrophages (MDM). GBS induced stronger IFN beta and TNF production as well as IRF5 nuclear translocation compared to S. aureus grown to the stationary phase, while S. aureus in exponential growth appeared similarly potent to GBS. Cytokine induction in primary human monocytes by GBS was not dependent on hemolysins, and induction of IFN beta and IL-12 as well as IRF5 activation were reduced with TLR2 ligand costimulation. Heat inactivation of GBS reduced IRF5 and NF-kB translocation, while only the viable E. coli activated IRF5. The attenuated stimulation correlated with loss of bacterial RNA integrity. The E. coli-induced IRF5 translocation was not inhibited by TLR2 costimulation, suggesting that IRF5 was activated via a TLR8-independent mechanism. Gene silencing of MDM using siRNA revealed that GBS-induced IFN beta, IL-12-p35, and TNF production was dependent on TLR8 and IRF5. In contrast, cytokine induction by E. coli was TLR8 independent but still partly dependent on IRF5. We conclude that TLR8-IRF5 signaling is more important for the sensing of GBS than for stationary grown S. aureus in human primary monocytes and MDM, likely due to reduced resistance of GBS to phagosomal degradation and to a lower production of TLR2 activating lipoproteins. TLR8 does not sense viable E. coli, while IRF5 still contributes to E. coli-induced cytokine production, possibly via a cytosolic nucleic acid sensing mechanism.

Background This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. Methods A meta-analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG + GG) and dominant model (TT + TG vs GG). Results A total of 28 comparisons were identified, including 11 228 SLE cases and 14 374 controls. Meta-analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR] = 1.393, 95% CI: 1.276-1.522, P < 0.001). Stratification by ethnicity indicated strong associations between T allele and SLE in Asians, Europeans and Latin Americans (OR = 1.256, 95% CI: 1.073-1.469, P = 0.004; OR = 1.338, 95% CI: 1.080-1.659, P = 0.008; OR = 1.853, 95% CI: 1.488-2.308, P < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.999, 95% CI: 1.442-2.771, P < 0.001; OR = 1.544, 95% CI: 1.009-2.362, P < 0.045). In addition, we found significant associations between the dominant model and SLE in all populations and Asians (OR = 1.521, 95% CI: 1.257-1.841, P < 0.001; OR = 1.270, 95% CI: 1.136-1.421, P < 0.001). A marginal association was detected between the recessive mode and SLE in overall subjects (OR = 1.480, 95% CI: 1.022-2.144, P = 0.038). Conclusion The current study suggested that individuals carrying rs2004640 T allele correlated with a high risk of SLE, and the IRF5 rs2004640 polymorphism was associated with SLE susceptibility.