title: Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacter rodentium.
abstract: Dendritic cells (DCs), monocytes, and macrophages are closely related phagocytes that share many phenotypic features and, in some cases, a common developmental origin. Although the requirement for DCs in initiating adaptive immune responses is well appreciated, the role of monocytes and macrophages remains largely undefined, in part because of the lack of genetic tools enabling their specific depletion. Here, we describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. Although neither cell type was required to initiate immunity, monocytes and macrophages contributed to the adaptive immune response by secreting IL-12, which induced Th1 polarization and IFN-γ secretion. Thus, whereas DCs are indispensable for priming naive CD4(+) T cells, monocytes and macrophages participate in intestinal immunity by producing mediators that direct T cell polarization.
authors.affiliation: Laboratory of Molecular Immunology, 2 Mucosal Immunology and 3 Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Schreiber
authors.forename: Jakob
authors.initials: J
authors.lastname: Loschko
authors.forename: Roos A
authors.initials: RA
authors.lastname: Karssemeijer
authors.forename: Amelia
authors.initials: A
authors.lastname: Escolano
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Meredith
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.forename: Pierre
authors.initials: P
authors.lastname: Guermonprez
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D044082:Citrobacter rodentium / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000276:immunology; D023061:Gene Order; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009113:Muramidase / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D018664:Interleukin-12; D016186:Receptor, Macrophage Colony-Stimulating Factor; D009113:Muramidase
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