Single-Cell Profiling Reveals a Conserved Role for Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection

Authors

Zachary Van Roy, University of Nebraska Medical CenterFollow
Gunjan Kak, University of Nebraska Medical CenterFollow
Lee E. Korshoj, University of Nebraska Medical CenterFollow
Joseph P. Menousek, University of Nebraska Medical Center
Cortney E. Heim, University of Nebraska Medical Center
Rachel W. Fallet, University of Nebraska Medical CenterFollow
James Campbell, University of Nebraska Medical CenterFollow
Carol Reynolds Geary, University of Nebraska Medical CenterFollow
Bo Liu, University of Nebraska Medical CenterFollow
Santhi Gorantla, University of Nebraska Medical CenterFollow
Larisa Y Poluektova, University of Nebraska Medical CenterFollow
Bin Duan, University of Nebraska Medical CenterFollow
Walter S. Campbell, University of Nebraska Medical CenterFollow
William Thorell, University of Nebraska Medical CenterFollow
Tammy Kielian, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Cell Reports Medicine

Publication Date

2024

Abstract

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The importance of HIF signaling was validated using a mouse model of Staphylococcus aureus craniotomy infection, where HIF inhibition increases chemokine production and leukocyte recruitment, exacerbating tissue pathology. These findings establish conserved metabolic and transcriptional signatures that may represent promising future therapeutic targets for human craniotomy infection in the face of increasing antimicrobial resistance.

DOI Link

10.1016/j.xcrm.2024.101790

ISSN

2666-3791

Creative Commons License

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

Recommended Citation

Van Roy, Zachary; Kak, Gunjan; Korshoj, Lee E.; Menousek, Joseph P.; Heim, Cortney E.; Fallet, Rachel W.; Campbell, James; Geary, Carol Reynolds; Liu, Bo; Gorantla, Santhi; Poluektova, Larisa Y; Duan, Bin; Campbell, Walter S.; Thorell, William; and Kielian, Tammy, "Single-Cell Profiling Reveals a Conserved Role for Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection" (2024). Journal Articles: Pathology and Microbiology. 109.
https://digitalcommons.unmc.edu/com_pathmicro_articles/109