Hormonal rewiring of immunity during dietary restriction ensures host defense and systemic glucose conservation
Access to this document is restricted. Some items have been embargoed at the request of the author, but will be made publicly available after the "No Access Until" date.
During the embargo period, you may request access to the item by clicking the link to the restricted file(s) and completing the request form. If we have contact information for a Cornell author, we will contact the author and request permission to provide access. If we do not have contact information for a Cornell author, or the author denies or does not respond to our inquiry, we will not be able to provide access. For more information, review our policies for restricted content.
Food shortages and infectious diseases were constant threats throughout mammalian evolution and often occurred simultaneously. When food availability is reduced, it is unclear how the host adapts to support glucose-demanding immune processes while preventing hypoglycemia. In the context of dietary restriction (DR), we found that glucocorticoids (GCs) aligned naive, effector, and memory T cell populations with the nutritional status of the host. DR-induced GCs promoted naive T cell homing to the bone marrow, which supported their homeostasis at steady state. Following a primary infection, DR-induced GCs rewired immunity to simultaneously uphold pathogen control and systemic glucose homeostasis. GCs achieved this by dampening effector T cells and enhancing the response of neutrophils with reduced glucose dependence. Although the total effector T cell pool was decreased during DR, GCs enriched memory-precursor effector cells to preserve memory formation. Thus, GCs align immunity and metabolic physiology to ensure host fitness when food availability is reduced.