Epstein Barr virus inhibits the stimulatory effect of TLR7/8 and TLR9 agonists but not CD40 ligand in human B lymphocytes

Abstract

Viruses and other microorganisms express specific pathogen-associated molecular patterns that are recognized by cell surface or endosome-associated Toll-like receptors (TLR). There are many examples of viruses that have developed strategies to modulate TLR signaling through the use of viral or cellular molecules. Epstein-Barr virus (EBV) has recently been found to display a complex interaction with TLR. The aim of this study was to asses the effect of EBV infection on proliferative capacity of TLR7/8 and 9 agonist and CD40 ligand (CD40L) in normal B lymphocytes. Our results demonstrate that EBV induces a significant inhibition in proliferative response to TLR7/8 (P < 0.004) and TLR9 (P < 0.000) agonists but not to CD40L stimulation in enriched human normal B lymphocytes. Similar inhibitory effect was also observed in B lymphocytes prestimulated with the TLR agonists, implying that the suppressive effect is not due to downregulation of TLR protein expression by EBV. EBV infection did not induce apoptosis and did not downregulate TLR7/8 mRNA expression in B lymphocytes. Our results suggest that EBV might be able to evade the immune system by modulation of the TLR signaling pathway.

Increased Frequency of CD8+and CD4+Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

“…B cells were stimulated with 5 μg/mL CpG-2006 (Operon Technologies, Stockholm, Sweden), a Toll-like receptor (TLR)-9 agonist, as previously described (32). A total number of 10 4 CD4 + CD25 + purified Tregs were also cultured concomitantly in 200 μL of complete culture medium and incubated in 96-well flat-bottom plates in triplicate for 36 hr.…”

Comparative human and mouse antibody responses against tetanus toxin at clonal level

“…Human LCL producing TeNT specific antibodies were established using an Epstein-Barr virus (EBV) transformation method as described elsewhere (Younesi et al, 2010). In brief, human B-cells were isolated from peripheral blood of normal subjects immunized with tetanus vaccine (Razi Vaccine and Serum Research Institute, Karaj, Iran) using magnetic-activated cell sorting (MACS) negative selection kits (Miltenyi Biotec, Bergisch Gladbach, Germany).…”

“…The clonality of the anti-TeNT antibodies produced by selected LCL was evaluated based on the Poisson statistical analysis as previously described (Younesi et al, 2010. This analysis states that, when a population of cells carrying an undefined number of antigen-specific precursors is randomly and independently distributed by limiting dilution among a number of wells, if more than 37% of wells at a given cell dilution (density) are negative for presence of antigen (i.e.…”

Innate Immune Recognition of EBV

“…EBV was furthermore reported to induce a significant inhibition of the proliferative responses of PBMC or enriched B cells to TLR9 or TLR7/8 agonists (Younesi et al 2010). The proliferation was described to be independent of the timepoint of EBV exposure before or after TLR triggering, suggesting that the suppressive effect was not due to EBV-induced downregulation of TLR protein expression.…”