Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen.
Marta M WegorzewskaRobert W P GlowackiSamantha A HsiehDavid L DonermeyerChristina A HickeyStephen C HorvathEric C MartensThaddeus S StappenbeckPaul M AllenPublished in: Science immunology (2020)
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.
Keyphrases
- regulatory t cells
- poor prognosis
- transcranial magnetic stimulation
- working memory
- binding protein
- lymph node
- physical activity
- dendritic cells
- weight loss
- immune response
- high glucose
- oxidative stress
- long non coding rna
- high frequency
- type diabetes
- squamous cell carcinoma
- protein protein
- adipose tissue
- risk assessment
- insulin resistance
- radiation therapy
- small molecule
- high fat diet induced
- wild type
- glycemic control