title: Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity.
abstract: Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node. As a consequence, canonical mucosal immune functions, including tolerance and protective immunity, are persistently compromised. Post-resolution of infection, signals derived from the microbiota maintain inflammatory mesentery remodeling and consequently, transient ablation of the microbiota restores mucosal immunity. Our results indicate that persistent disruption of communication between tissues and the immune system following clearance of an acute infection represents an inflection point beyond which tissue homeostasis and immunity is compromised for the long-term. VIDEO ABSTRACT.
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA; Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, 14049-900, Brazil.
authors.forename: Denise Morais da
authors.initials: DM
authors.lastname: Fonseca
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Hand
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Seong-Ji
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Arielle
authors.initials: A
authors.lastname: Glatman Zaretsky
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA; Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA; Department of Bioinformatics, Boston University, Boston, MA 02215, USA.
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Byrd
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Harrison
authors.affiliation: Program in Tissue Immunity and Repair and Immunopathogenesis Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Bioinformatics and Computational Bioscience Branch, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Mariam
authors.initials: M
authors.lastname: Quinones
authors.affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.affiliation: Program in Tissue Immunity and Repair and Immunopathogenesis Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD 20892, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH), Bethesda, MD 20892, USA; Immunity at Barrier Sites Initiative, NIAID/NIH, Bethesda, MD 20892, USA. Electronic address: ybelkaid@niaid.nih.gov.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D002465:Cell Movement; D002908:Chronic Disease; D003713:Dendritic Cells / Q000473:pathology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007154:Immune System Diseases / Q000382:microbiology* / Q000473:pathology*; D008206:Lymphatic Diseases / Q000382:microbiology / Q000473:pathology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000276:immunology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D015011:Yersinia pseudotuberculosis / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology* / Q000473:pathology