Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Novel approaches to retrieve and enhance immunity against cancer antigens have been established. One promising approach involves the use of virus particles derived from the plant virus, Cowpea Mosaic Virus (CPMV). Injection of CPMV into tumor stimulates systemic antitumor immunity in tumor mouse models and canine patients with tumors. The molecular pathways that account for these effects are not well defined. In these studies, we examine the capacity of CPMV to activate human monocytes. Peripheral blood mononuclear cells were incubated overnight with CPMV and CD14+ monocytes were examined by flow cytometry for expression of various markers. Cells were also incubated with “empty” (RNA-free) CPMV (eCPMV) for comparison. Responses to CPMV were also tested with THP-1 dual reporter cells, which are activated by various surface and cytoplasm pattern recognition receptors ligands except for TLR7. CPMV, but not eCPMV, mediated activation of human monocytes as indicated by induced expression of CD86, PDL-1, HLA-DR, IL-15R, and IP-10. In contrast to positive controls, PAM3CSK4 (TLR1/2 agonist) and LPS (TLR4 agonist), neither CPMV nor eCPMV induced activation of THP-1 cells. Activation of monocytes by CPMV was markedly inhibited by a chemical inhibitor of spleen tyrosine kinase (SYK), a key signaling component of TLR activation pathways. Effects of SYK inhibition were also observed in cells stimulated by a TLR7 agonist, imiquimod, but with different outcomes than CPMV stimulation, depending on the activation index that was assessed. These data demonstrate that CPMV activates monocytes in a manner that is highly dependent on RNA and SYK signaling. Overall, these data raise the possibility that TLR7 may play a role in CPMV adjuvant-like activity.</jats:p>