Toll-like receptor 2 ligands enhance monocyte Fcγ receptor function (68.16)

Abstract

Abstract Fcγ receptors (FcγR) are major effectors of antibody therapy so it is critical to seek new ways to enhance their effectivness. Toll-like receptors (TLR) recognize a wide range of microbial components, eliciting cellular responses such as cytokine production and generation of antimicrobial factors. Among these receptors, TLR2 recognizes both bacterial and fungal components. Given the strong cellular proinflammatory responses to TLR2 activation, we explored the possibility that TLR2 agonists could strengthen FcγR activity. Human peripheral blood monocytes (PBM) were treated with or without the TLR2 agonist PAM2CSK4 and tested for FcγR expression and function. Results showed that overnight treatment with PAM2CSK4 led to an increase in the expression of both FcγRIIa and the common γ-subunit, while expression of the inhibitory receptor FcγRIIb remained unchanged. Along with this, PAM2CSK4 significantly increased IgG-mediated TNFα production in plate-bound assays. We then tested its effect on phagocytosis, using fluorescently-labeled opsonized sheep red blood cells as targets. PAM2CSK4 significantly enhanced the phagocytic ability of PBM. To test the effect of PAM2CSK4 in vivo, we injected it in combination with anti-CD20 antibody and measured B-cell depletion. Results showed that PAM2CSK4 led to greater depletion of splenic B cells. These findings suggest that TLR2 agonists modulate FcγR expression and function and should be investigated as possible adjuvants for antibody therapy.