Professor Midwestern Univ., Downers Grove Downers Grove, Illinois, United States
Disclosure(s):
Michelle Swanson-Mungerson, PhD: No financial relationships to disclose
Introduction/Rationale: Toll-like receptor 9 (TLR9) in an important mechanism by which both innate and adaptive immune cells sense unmethylated DNA of bacteria and viruses. Epstein-Barr virus (EBV) is a double-stranded DNA enveloped virus that infects both epithelial cells and B cells. Since B cells express TLR9, we sought to determine if the latency protein, LMP2A, from EBV would impact TLR9 expression and/or function.
Methods: BJAB B cell lymphoma cells stably transfected with either vector, wildtype LMP2A or forms of LMP2A that harbor mutations in the N-terminal signaling tail were analyzed for TLR9 levels by flow cytometry. Additionally, these cells were stimulated with the TLR9 agonist, agatolimod (ODN2006), and the production of IL-6 was assessed by ELISA.
Results: The data indicate that LMP2A does not consistently alter TLR9 levels, but does enhance TLR9-induced cytokines, such as IL-6. The mechanism by which LMP2A confers this enhancement is currently under investigation.
Conclusion: TLR9 is an important innate sensing mechanism to identify the presence of pathogen’s DNA intracellularly. The ability of EBV to modulate signaling through these receptors may provide insight into mechanisms by which latency proteins regulate latency and B cell activation.
