Macaque and human pDC were shown to have similar TLR expression profiles [25], which is in agreement with the response patterns observed by us. Also TLR-7, TLR-9 and myeloid differentiation primary response gene 88 (MYD88) Selleckchem EX527 sequences were shown to be identical, whereas there were important differences for interferon regulatory factor 7 (IRF-7) [26]. Other regulatory pathways still need to be explored [37]. Beside TLRs, the C-type lectin receptor (CLR) family plays an important role in the modulation of innate immune responses [38, 39]. Human pDC express the CLRs blood dendritic cell antigen 2 (BDCA2) and dendritic cell immunoreceptor (DCIR) [40]. Cross-linking of DCIR was shown to result in reduced IFN-α induction upon

TLR-9 stimulation [40], and similar inhibitory effects were reported following incubation with the CLR ligand mannan [41]. Interestingly, BDCA2 [our unpublished observation and documented at the NIH non-human primate reagent resource portal (http://nhpreagents.bidmc.harvard.edu/NHP)] and DCIR [42] were shown to be absent on pDC in rhesus macaques. Although not investigated here, a difference in the balance between activating TLRs and inhibitory CLRs could lead to different levels of pDC activation, possibly translating into a difference in cytokine production pattern. A direct comparison between the absolute numbers of pDC, mDC and monocytes in rhesus versus human blood showed that rhesus

macaques had a lower number of pDC, while learn more there was no difference in the abundance of the other subsets. The number

of pDC observed, i.e. 3020 ± 1357 cells/μl, is in agreement with several reports on rhesus macaques [16, 18, 24, 25, 43] and considerably less ID-8 than in humans [44]. In contrast, two other studies, where a direct head-to-head comparison was made, showed no difference in pDC number [17, 28], although it must be noted that in those studies the quantification was either performed on PBMC or cynomolgus monkeys imported from Mauritius were used, which have a more limited genetic diversity and might differ from rhesus macaques. The strong IL-12p40 expression in rhesus pDC may have implications for preclinical evaluation of vaccines in this model. For instance, TLR-7/8 containing adjuvants might trigger different responses in macaques than in humans and involve pDC as IL-12 producing cells. Also TLR-9 agonists could be expected to induce an IL-12 response in rhesus macaques, in contrast to humans. Simultaneous production of IFN-α and the inflammatory cytokines TNF-α and T helper type 1 (Th1)-skewing cytokine IL-12 might also lead to a slightly different response pattern to bacterial and viral infection and have consequences for the induction of CD8 responses [45, 46]. We would like to thank Dr F. Verreck for critical reading of the manuscript, Dr S.B. Geutskens for organizing the collection of the human blood samples and H. van Westbroek for preparing the figures.