Alterations in host metabolic state have been reported to drastically alter gut microbial communities and influence host immune responses. While much attention has been paid to how the gut microbiome affects immune cell response, the reverse is understudied: how do immune cells influence the gut microbiome and in turn, regulate host metabolic state? CD11c+ cells are well known for their critical role in bridging innate and adaptive immune responses and are resident cells of almost all tissues in the body. In the gut, CD11c+ cells are located in the lamina propria and have been shown to play a key role in maintaining gut immune homeostasis. The tuberous sclerosis 1 - mechanistic target of rapamycin complex 1 (Tsc1-mTORC1) pathway is a cell’s major nutrient-sensing pathway and functions to assess nutrient availability and determine whether energy-intensive processes, such as protein translation, should take place. Specifically, Tsc1 is a negative regulator of mTORC1 and inhibits mTOR activity under conditions of low nutrient availability. Given this knowledge, we asked whether perturbing nutrient sensing in CD11c+ cells would alter the gut microbiome to ultimately influence host systemic metabolism. We generated CD11cCre x Tsc1flox/flox mice (C57BL/6J background), where Tsc1 was specifically deleted in all CD11c expressing cells. Tsc1flox/flox (“control; CTRL”) and CD11cCre x Tsc1flox/flox (“knockout; KO”) mice were housed under thermoneutral (30°C) and sub-thermoneutral conditions (22°C), and placed on normal chow diet (NCD) or high-fat diet (HFD). Weight gain, glucose and insulin sensitivity, and food intake were monitored over time. Additionally stool was collected for 16S rRNA gene sequencing. First, we determined how nutrient sensing by immune cells regulates body weight, adiposity and insulin action. Under all housing conditions, KO mice exhibited reduced weight gain as compared to CTRL mice. This decrease in body weight was not due to growth or birth defects and persisted with age. Analysis of food intake uncovered a reduction in overall food consumption. There were no differences in metabolic rate or physical activity between the groups. Interestingly, on a HFD protection from insulin resistance only occurred under thermoneutral conditions. In addition, we have investigated the microbial and immunologic mechanisms by which alterations in nutrient sensing in immune cells regulates weight gain. Flow cytometric analyses of immune cell populations in the small intestine and colon revealed differences in IgA binding. Co-housing experiments identified KO as capable of gaining weight in the presence of the CTRL mouse microbiome. Conclusions: We show that activation of nutrient sensing pathways in CD11c+ cells is sufficient to modulate systemic metabolism through alterations in the gut microbiome and that housing temperature conditions affects insulin and the microbiome. This project furthers our understanding of the role immune cells play in regulating systemic metabolism and has immediate translational implications for the treatment of metabolic disorders.