title: Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection.
abstract: Tissue-infiltrating Ly6C(hi) monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DCs) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals after tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Askenase
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Seong-Ji
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Byrd
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Morais da Fonseca
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wilhelm
authors.affiliation: Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK; Faculty of Life Sciences, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Konkel
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Hand
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Norinne
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
authors.affiliation: Laboratory of Experimental Immunology, Head, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Manchester Collaborative Centre for Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK; Faculty of Life Sciences, University of Manchester, Manchester M13 9NT, UK. Electronic address: john.grainger-2@manchester.ac.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.affiliation: Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000469:parasitology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000469:parasitology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D009928:Organ Specificity / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D050976:Basic-Leucine Zipper Transcription Factors; C494192:Ly-6C antigen, mouse; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D018664:Interleukin-12; D007371:Interferon-gamma