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Sci Immunol. 2019 Feb 8;4(32). pii: eaau9079. doi: 10.1126/sciimmunol.aau9079.

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
2
Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA.
3
Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
4
Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA. pallen@wustl.edu stappeb@wustl.edu emartens@umich.edu.
5
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA. pallen@wustl.edu stappeb@wustl.edu emartens@umich.edu.

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, BθOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BθOM 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 BθOM 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 BθOM 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.

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