The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1-cDC2) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen presenting cells (APC). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of Fc receptor CD64 shared with MCs, and of IRF8 shared with cDC1s. These inflammatory (Inf-)cDC2s were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2 matured in response to cell-intrinsic toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module and acquired antigens via convalescent serum and Fc receptors. Since hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

Cedric Bosteels, Katrijn Neyt, Manon Vanheerswynghels, Mary J. van Helden, Dorine Sichien, Nincy Debeuf, Sofie De Prijck, Victor Bosteels, Niels Vandamme, Liesbet Martens, Yvan Saeys, Els Louagie, Manon Lesage, David L. Williams, Shiau-Choot Tang, Johannes U. Mayer, Franca Ronchese, Charlotte L. Scott, Hamida Hammad, Martin Guilliams and Bart N. Lambrecht. Inflammatory type 2 conventional dendritic cells (cDC2s) acquire characteristics of cDC1s and macrophages to orchestrate immunity to respiratory virus infection. Immunity, 2020.

These results were obtained in the teams of Bart N. Lambrecht and Martin Guilliams, at the VIB inflammation research center. The online tool was developed by the group of Yvan Saeys. We hope you will find this resource useful and we would be happy to hear about your experiences and suggestions.