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• The immune system and the gut microbiota: friends or foes?

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         description:Polly Matzinger and her colleagues have shown that in the absence of B cells, and in the presence of the microbiota, the intestinal epithelium launches its own immune defense mechanisms. However, this comes at the expense of metabolic programs involved in fat absorption by the gut. These results could explain the lipid malabsorption often seen in humans with common variable immunodeficiency or with HIV infection. Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell–deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.
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            name:Comparative Medicine Branch, NIAID, NIH
            address:
               name:Comparative Medicine Branch, NIAID, NIH, Bethesda, USA
               type:PostalAddress
            type:Organization
      name:Lloyd Mayer
      affiliation:
            name:Immunology Institute, Mount Sinai Medical Center
            address:
               name:Immunology Institute, Mount Sinai Medical Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Andrew J Macpherson
      affiliation:
            name:University of Bern
            address:
               name:University of Bern, Bern, Switzerland
               type:PostalAddress
            type:Organization
      name:Kathy D McCoy
      affiliation:
            name:University of Bern
            address:
               name:University of Bern, Bern, Switzerland
               type:PostalAddress
            type:Organization
            name:Farncombe Family Digestive Health Research Institute, McMaster University
            address:
               name:Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
               type:PostalAddress
            type:Organization
      name:Claire Fraser-Liggett
      affiliation:
            name:Institute for Genome Sciences, University of Maryland School of Medicine
            address:
               name:Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, USA
               type:PostalAddress
            type:Organization
      name:Polly Matzinger
      affiliation:
            name:'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH)
            address:
               name:'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, USA
      name:Present address: College of Pharmacy, Oregon State University, Corvallis, Oregon, USA.,
      name:'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, USA
      name:Present address: College of Pharmacy, Oregon State University, Corvallis, Oregon, USA.,
      name:Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, USA
      name:Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, USA
      name:Mucosal Immunology Section, Laboratory of Host Defenses, NIAID, NIH, Bethesda, USA
      name:Mouse Metabolism Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA
      name:Comparative Medicine Branch, NIAID, NIH, Bethesda, USA
      name:Immunology Institute, Mount Sinai Medical Center, New York, USA
      name:University of Bern, Bern, Switzerland
      name:University of Bern, Bern, Switzerland
      name:Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
      name:Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, USA
      name:'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, USA
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

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