MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health

Details

• Alternative Title:
  Cell Host Microbe
• Personal Author:
  Kubinak, Jason L. ; Petersen, Charisse ; Stephens, W. Zac ; Soto, Ray ; Bake, Erin ; O’Connell, Ryan M. ; Round, June L.
• Description:
  Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis.
• Subjects:
  Adaptive Immunity Animals Article B-Lymphocytes Gastrointestinal Microbiome Homeostasis Immunity, Innate Immunoglobulin A Intestinal Mucosa Mice Myeloid Differentiation Factor 88 Signal Transduction T-Lymphocytes

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• Source:
  Cell Host Microbe. 2014; 17(2):153-163.
• Pubmed ID:
  25620548
• Pubmed Central ID:
  PMC4451207
• Document Type:
  Journal Article
• Funding:
  1S10RR026802-01/RR/NCRR NIH HHS/United States ; 5-P39-DK034987/DK/NIDDK NIH HHS/United States ; 5-P40-OD010995/OD/NIH HHS/United States ; AI107090/AI/NIAID NIH HHS/United States ; AI109122/AI/NIAID NIH HHS/United States ; DP2 AT008746/AT/NCCIH NIH HHS/United States ; DP2AT008746-01/AT/NCCIH NIH HHS/United States ; DP2GM111099-01/DP/NCCDPHP CDC HHS/United States ; K22 AI095375/AI/NIAID NIH HHS/United States ; K22 AI95375/AI/NIAID NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R00HL102228-05/HL/NHLBI NIH HHS/United States ; R21 AI109122/AI/NIAID NIH HHS/United States ; T32 AI-055434/AI/NIAID NIH HHS/United States ; T32 GM007464/GM/NIGMS NIH HHS/United States
• Volume:
  17
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b4ab7e4c0092bf92de2a31fc771dd94ef695e6688bf77ef276a39d4f9fd98b32
• Download URL:
  https://stacks.cdc.gov/view/cdc/31395/cdc_31395_DS1.pdf
• File Type:
  [PDF - 935.42 KB ]