MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health
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Published Date:Jan 22 2015
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Publisher's site:
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Source:Cell Host Microbe. 2014; 17(2):153-163.
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Personal Authors:
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Keywords:
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Pubmed ID:25620548
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Pubmed Central ID:PMC4451207
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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 TÂ 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 TÂ 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 TÂ cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis.
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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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