Abstract
Abstract TLR7 and TLR8 are located on endosomal membranes and function to detect ssRNA released by viral or bacterial pathogens. Differences in the response characteristics of these two receptors, in terms of cell type preference and cytokine profile of human PBMC was being revealed. However, the effect of these two agonists on the same cell still remains as a question. Human monocytes express both TLR7 and TLR8 are highly plastic cells which is an important feature for immunotherapies. This study investigates the effects of TLR7 and 8 agonists on human classical monocytes in terms of activation and differentiation into macrophages. CD14+ HLA DR+ monocytes from healthy donors were cultured with the TLR7 specific agonist 3M-055, TLR8 specific agonist CL-075, and TLR7/8 dual agonist R848. All three agonists induced human monocytes to mature into macrophage significantly when compared to the unstimulated monocytes. A majority of those macrophages were 25F9+/CD200R−/CD206+ with an increased CD163 expression observed only with TLR8 agonists. Although CD163 and CD206 are commonly expressed on M2-like macrophage, functional analysis revealed that the macrophages differentiated by TLR7 or TLR8 agonists overall does not have significant endocytic ability (a prominent M2-macrophage function). TLR8 stimulation resulted in prominent pro-inflammatory cytokine increase whereas TLR7 agonist stimulation did not. Furthermore, TLR7 agonists decreased the cytokine induction by TLR8 agonists and this decrease was more prominent when TLR7 agonists were given prior to the TLR8 agonist. This study reveals differences in TLR7 vs TLR8 response of the monocytes and regulatory role of TLR7 on TLR8.
Published Version
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