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

• Published in: Science immunology Vol. 4; no. 32
• Main Authors: Wegorzewska, Marta M, Glowacki, Robert W P, Hsieh, Samantha A, Donermeyer, David L, Hickey, Christina A, Horvath, Stephen C, Martens, Eric C, Stappenbeck, Thaddeus S, Allen, Paul M
• Format: Journal Article
• Language: English
• Published: United States 08.02.2019
• Subjects: Adoptive Transfer - methods; Animals; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Bacterial Proteins - metabolism; Bacteroides thetaiotaomicron - immunology; Cell Differentiation - immunology; Colitis - immunology; Colitis - prevention & control; Colon - immunology; Culture Media; Diet; Escherichia coli - immunology; Glucose - metabolism; Hybridomas - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nutrients - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; T-Lymphocytes, Regulatory - immunology
• DOI: 10.1126/sciimmunol.aau9079

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 ( ). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in colonized healthy mice and differentiated into regulatory T cells (T ) and effector T cells (T ). Depletion of -specific T resulted in colitis, showing that a single protein expressed by can drive differentiation of T that self-regulate T to prevent disease. We found that BθOM T cells recognized a peptide derived from a single 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.