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MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health
Filetype[PDF - 935.42 KB]


Details:
  • Personal Authors:
  • Keywords:
  • Pubmed ID:
    25620548
  • Pubmed Central ID:
    PMC4451207
  • 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.

  • Document Type:
    Journal Article
  • Collection(s):
    CDC Public Access
  • 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
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