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

Kubinak, Jason L.; Petersen, Charisse; Stephens, W. Zac; Soto, Ray; Bake, Erin; O’Connell, Ryan M.; Round, June L.

doi:10.1016/j.chom.2014.12.009

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

Published Date:

Jan 22 2015

Publisher's site:

http://dx.doi.org/10.1016/j.chom.2014.12.009 New Site Icon

Source:

Cell Host Microbe. 2014; 17(2):153-163.

[PDF-935.42 KB]

Details:

Personal Authors:

Kubinak, Jason L. ; Petersen, Charisse ; Stephens, W. Zac ; Soto, Ray ; Bake, Erin ; ... More ▼

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:

Supporting Files:

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