The Journal of Experimental Medicine ARTICLE The Rockefeller University Press $30.00 J. Exp. Med. Vol. 206 No. 3 595-606 www.jem.org/cgi/doi/10.1084/jem.20081385 595 Monocytes, macrophages, and DCs form net- works of phagocytic cells throughout most tis- sues, the development of which are dependent on the CSF-1 receptor (csf1r, also known as CD115, c-fms, and M-CSF receptor) (1, 2). These cells, which are sometimes referred to as the mononuclear phagocyte system, play major roles in development, scavenging, inlammation, and antipathogen defenses (3, 4). They are highly heterogeneous in phenotype, tissue distribution, and function (3, 5, 6). Considerable attention is currently focused on the characterization of their progenitors and precursors, the signals driving their development in the BM, their migration to tissues, and their homeostasis in peripheral tis- sues. CSF-1R and its two known ligands, M-CSF and IL34 (7), are critical for the development of this lineage because M-CSF–deicient mice (op/ op and csf1 -/ - ) have a milder phenotype than the Csf1r-deicient mice (8). Other cytokines, such as GM-CSF, FLT3, LT- 1 2 (LT- ) (9–15), and chemokines (16, 17) have also been shown to control the development and homeo- stasis of the macrophage and DC networks. Cellular cloning and transplantation studies have shown that many macrophage subsets, most of the conventional DCs (cDCs) in the second- ary lymphoid organs of mice, and at least a frac- tion of the DCs in the mouse thymus probably originate from myeloid progenitors (18–20). CORRESPONDENCE Frederic Geissmann: frederic.geissmann@kcl.ac.uk Abbreviations used: cDC, con- ventional DC; CDP, common DC precursor; GMP, granulo- cyte-macrophage progenitors; iNOS, inductible nitric oxide synthase; Lm, Listeria monocyto- genes; MDP, macrophage/DC precursor; PDC, plasmacytoid DC; PI, propidium iodide; ROI, reactive oxygen intermediate. C. Aufray, D.K. Fogg, and E. Narni-Mancinelli contributed equally to this paper. CX 3 CR1 + CD115 + CD135 + common macrophage/DC precursors and the role of CX 3 CR1 in their response to inlammation Cedric Aufray , 1 Darin K. Fogg, 1 Emilie Narni-Mancinelli, 2 Brigitte Senechal, 1 Celine Trouillet, 1,3 Noah Saederup , 4 Julia Leemput, 5 Karine Bigot, 5 Laura Campisi, 2 Marc Abitbol, 5 Thierry Molina, 1 Israel Charo , 4 David A. Hume, 6 Ana Cumano, 7 Gregoire Lauvau, 2 and Frederic Geissmann 1,3 1 Laboratory of Biology of the Mononuclear Phagocyte System, Institut National de la Santé et de la Recherche Médicale (INSERM) U838, Université Paris-Descartes, 75015 Paris, France 2 INSERM U924, Université de Nice-Sophia Antipolis, 06560 Valbonne, France 3 Centre for Inlammation Biology, Division of Immunity, Infection, and Inlammatory Diseases, King’s College London, SE1 9RT London, England, UK 4 Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94158 5 Centre d’etude et de recherche therapeutique en ophtalmologie, Université Paris-Descartes, 75015 Paris, France 6 The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, EH25 9PS Roslin, Scotland, UK 7 INSERM U668, Unité de Développement des Lymphocytes, Institut Pasteur, 75015 Paris, France CX 3 CR1 expression is associated with the commitment of CSF-1R + myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R + CX 3 CR1 + macrophage/DC precursor (MDP) with other DC precursors and the role of CX 3 CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to con- ventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1 + inlamma- tory monocytes that differentiate into TipDCs during infection. CX 3 CR1 deiciency selectively impairs the recruitment of blood Gr1 + monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs. © 2009 Auffray et al. This article is distributed under the terms of an Attribu- tion–Noncommercial–Share Alike–No Mirror Sites license for the irst six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncom- mercial–Share Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/). on March 18, 2013 jem.rupress.org Downloaded from Published March 9, 2009 http://jem.rupress.org/content/suppl/2009/03/10/jem.20081385.DC1.html Supplemental Material can be found at: