Expression and function of toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates

Abstract

Antigen presenting cells (APCs), especially dendritic cells (DCs), play a crucial role in immune responses against infections by sensing microbial invasion through toll-like receptors (TLRs). Thus, TLR ligands are attractive candidates for use in humans and animal models as vaccine adjuvants. So far, no studies have performed on TLR expression in non-human primates such as rhesus macaques. We therefore performed a comparative cross-species study on TLR expression patterns (TLR3, 4, 7, 8 and 9) of APCs in human, rhesus macaques and mice. We demonstrate that blood DC subsets of rhesus macaque expressed the same sets of TLRs as human DCs but substantially differed from mouse DC subsets. In macaque and human, myeloid DCs (MDCs) expressed TLR3, 4, 7 and 8 whereas plasmacytoid DCs (PDCs) expressed only TLR7 and 9, in contrast to mouse, both DC subsets expressed all TLRs (TLR3, 4, 7, 8 and 9). Additionally, TLR expression patterns in macaque monocyte-derived dendritic cells (mo-DCs) (i.e., TLR3, 4 and 8), monocytes (i.e., TLR4, 7, and 8) and B cells (i.e., TLR4, 7, 8, and 9) were also similar to their human counterparts. However, the responsiveness of macaque APCs to certain TLR ligands partially differed from those of human in terms of phenotype differentiation and cytokine production. Strikingly, in contrast to human mo-DCs, no IL-12p70 production was observed when macaque mo-DCs were stimulated with TLR ligands. Our results provide important information for a rational design of animal models in evaluating TLR ligands as adjuvant in vivo.