Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen

Marta M. Wegorzewska, Robert W.P. Glowacki, Samantha A. Hsieh, David L. Donermeyer, Christina A. Hickey, Stephen C. Horvath, Eric C. Martens, Thaddeus S. Stappenbeck, Paul M. Allen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B. theta–colonized healthy mice and differentiated into regulatory T cells (Tregs) and effector T cells (Teffs). Depletion of B. theta–specific Tregs resulted in colitis, showing that a single protein expressed by B. theta can drive differentiation of Tregs that self-regulate Teffs to prevent disease. We found that BOM T cells recognized a peptide derived from a single B. theta protein, BT4295, whose expression is regulated by nutrients, with glucose being a strong catabolite repressor. Mice fed a high-glucose diet had a greatly reduced activation of BOM T cells in the colon. These studies establish that the immune response to specific bacterial antigens can be modified by changes in the diet by altering antigen expression in the microbe.

Original languageEnglish
Article numbereaau9079
JournalScience immunology
Volume4
Issue number32
DOIs
StatePublished - 2019

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