Repeated Social Defeat Stress Leads to Immunometabolic Shifts in Innate Immune Cells of the Spleen

Authors

Mandakh Bekhbat, Emory University
John Drake, Texas A&M University
Emily C. Reed, Texas A&M University
Tatlock H. Lauten, Texas A&M University
Tamara Natour, Texas A&M University
Vladimir I. Vladimirov, Texas A&M University
Adam J. Case, Texas A&M UniversityFollow

Document Type

Article

Journal Title

Brain, Behavior, and Immunity - Health

Publication Date

2023

Volume

34

Abstract

Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p < 0.05) compared to NS littermates. RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). These results suggest that the metabolic enhancement reflected by upregulation of glycolytic and OXPHOS pathways may be important for cellular proliferation of splenic macrophages and granulocytes following repeated stress exposure. A better understanding of these intracellular metabolic mechanisms may ultimately help develop novel strategies to reverse the impact of stress and associated peripheral immune changes on the brain and behavior.

DOI Link

10.1016/j.bbih.2023.100690

ISSN

2666-3546

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Bekhbat, Mandakh; Drake, John; Reed, Emily C.; Lauten, Tatlock H.; Natour, Tamara; Vladimirov, Vladimir I.; and Case, Adam J., "Repeated Social Defeat Stress Leads to Immunometabolic Shifts in Innate Immune Cells of the Spleen" (2023). Journal Articles: Cellular & Integrative Physiology. 50.
https://digitalcommons.unmc.edu/com_cell_articles/50