title: Whole blood stimulation with Toll-like receptor (TLR)-7/8 and TLR-9 agonists induces interleukin-12p40 expression in plasmacytoid dendritic cells in rhesus macaques but not in humans.
abstract: Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation. Dendritic cells are important as key regulators of innate and adaptive immune responses. Using a new whole blood assay we investigated functional characteristics of blood plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC) and monocytes in rhesus macaques by studying induction of activation markers and cytokine expression upon Toll-like receptor (TLR) stimulation. In a head-to-head comparison we observed that rhesus macaque venous blood contained relatively lower numbers of pDC than human venous blood, while mDC and monocytes were present at similar percentages. In contrast to humans, pDC in rhesus macaques expressed the interleukin (IL)-12p40 subunit in response to TLR-7/8 as well as TLR-9 stimulation. Expression of IL-12p40 was confirmed by using different monoclonal antibodies and by reverse transcription-polymerase chain reaction (RT-PCR). Both in humans and rhesus macaques, TLR-4 stimulation induced IL-12p40 expression in mDC and monocytes, but not in pDC. The data show that, in contrast to humans, pDC in macaques are able to express IL-12p40, which could have consequences for evaluation of human vaccine candidates and viral infection.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Koopman
authors.forename: N
authors.initials: N
authors.lastname: Beenhakker
authors.forename: S
authors.initials: S
authors.lastname: Burm
authors.forename: O
authors.initials: O
authors.lastname: Bouwhuis
authors.forename: J
authors.initials: J
authors.lastname: Bajramovic
authors.forename: V
authors.initials: V
authors.lastname: Sommandas
authors.forename: G
authors.initials: G
authors.lastname: Mudde
authors.forename: P
authors.initials: P
authors.lastname: Mooij
authors.forename: B A
authors.initials: BA
authors.lastname: 't Hart
authors.forename: W M J M
authors.initials: WM
authors.lastname: Bogers
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008253:Macaca mulatta; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000097:blood*; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000097:blood*; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000097:blood*
chemical_list: D053762:Interleukin-12 Subunit p40; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9
keywords: Toll-like receptors (TLRs); animal models - non-human primates; cytokine/interleukin/chemokine receptors; dendritic cells (myeloid; monocyte-derived); plasmacytoid