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MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health
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Jan 22 2015
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Source: Cell Host Microbe. 2014; 17(2):153-163.
[PDF-935.42 KB]
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Alternative Title:Cell Host Microbe
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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 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.
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Pubmed ID:25620548
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Pubmed Central ID:PMC4451207
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Volume:17
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Issue:2
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