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Title: Phenotype and function of CD209+ bovine blood dendritic cells, monocyte-derived-dendritic cells and monocyte-derived macrophages

Author
item PARK, KUN TAEK - Seoul National University
item ELNAGGER, MAHMOUD - Alexandria University Of Egypt
item ABDELLRAZEQ, GABER - Alexandria University Of Egypt
item Bannantine, John
item MACK, VICTORIA - Washington State University
item Fry, Lindsay
item DAVIS, WILLIAM - Washington State University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2016
Publication Date: 10/20/2016
Citation: Park, K., Elnagger, M., Abdellrazeq, G., Bannantine, J.P., Mack, V., Fry, L.M., Davis, W.C. 2016. Phenotype and function of CD209+ bovine blood dendritic cells, monocyte-derived-dendritic cells and monocyte-derived macrophages. PLoS One. 11(10):e0165247. doi:10.14371/journal.pone.0165247.org/.

Interpretive Summary: It has been difficult to study bovine dendritic cells and their role in immune system functions. This is due at least in part to the lack of cell surface markers to categorize this cell group. In this report, a new monoclonal antibody that recoginzes the cell surface marker, CD209 has been developed. This antibody has provided a novel look at dentric cells and we discovered that dendritic cells in the blood as well as dendritic cells derived from monocytes are phenotypically linked. We further showed that protein antigens of Mycobacterium avium subspecies paratuberculosis (MAP), a bacterium that causes Johne's disease in cattle and sheep, are able to stimulate immune memory responses in both dendritic cell populations. These memory responses were also observed when stimulating with live MAP vaccine candidates. These results suggest an important role of dendritic cells in protective vaccination against MAP.

Technical Abstract: Phylogenic comparisons of the mononuclear phagocyte system (MPS) of humans and mice demonstrate phenotypic divergence of dendritic cell (DC) subsets that play similar roles in innate and adaptive immunity. Although differing in phenotype, DC can be classified into four groups according to ontogeny and function: conventional DC (cDC1 and cDC2), plasmacytoid DC (pDC), and monocyte derived DC (MoDC). DC of Artiodactyla (pigs and ruminants) can also be sub-classified using this system, allowing direct functional and phenotypic comparison of MoDC and other DC subsets trafficking in blood (bDC). Because of the high volume of blood collections required to study DC, cattle offer the best opportunity to further our understanding of bDC and MoDC function in an outbred large animal species. As reported here, DC phenotyping using a monoclonal antibody (mAb) to CD209 revealed CD209 is expressed on the major myeloid population of DC present in blood and MoDC, providing a phenotypic link between these two subsets. Additionally, the present study demonstrates that CD209 is also expressed on monocyte derived macrophages (MoF). Functional analysis revealed each of these populations can take up and process antigens (Ags), present them to CD4 and CD8 T cells, and elicit a T-cell recall response. Thus, bDC, MoDC, and MoF pulsed with pathogens or candidate vaccine antigens can be used to study factors that modulate DC-driven T-cell priming and differentiation.