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Cell. 2015 Oct 8;163(2):354-66. doi: 10.1016/j.cell.2015.08.030.

Microbiota-Dependent Sequelae of Acute Infection Compromise Tissue-Specific Immunity.

Author information

1
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.
2
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.
3
Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID/NIH, Bethesda, MD 20892, USA.
4
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.
5
Program in Tissue Immunity and Repair and Immunopathogenesis Section, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
6
Bioinformatics and Computational Bioscience Branch, NIAID/NIH, Bethesda, MD 20892, USA.
7
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
8
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
10
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.

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.

PMID:
26451485
PMCID:
PMC4826740
DOI:
10.1016/j.cell.2015.08.030
[Indexed for MEDLINE]
Free PMC Article

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