"Targeting Myeloid Cell Iron Metabolism in Salmonella-induced Colitis" by Mariella Arcos Padilla
 

Biomedical Engineering ETDs

Publication Date

Fall 12-15-2024

Abstract

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality.

Previous studies have shown that mice lacking the iron storage protein ferritin heavy chain (FTH1) in myeloid cells exhibit worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) directs FTH1 autophagic degradation to release iron from storage during conditions of low iron. However, the role of myeloid NCOA4 in regulating bacterial infections remains unclear.

Here, we found that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages (BMDM) cells. This deficiency also increases susceptibility to Salmonella-induced colitis in mice due to exacerbated oxidative stress and ferroptosis.

Our results not only give us a better understanding of myeloid iron metabolism but also pave the way for novel myeloid cell-targeted therapies to combat salmonellosis.

Language

English

Keywords

Iron, macrophages, oxidative stress, NCOA4, Nrf2, Keap1, Salmonella

Document Type

Dissertation

Degree Name

Biomedical Engineering

Level of Degree

Doctoral

Department Name

Biomedical Engineering

First Committee Member (Chair)

Xiang Xue

Second Committee Member

Curt Hines

Third Committee Member

Achraf Noureddine

Fourth Committee Member

Sungjin Kim

Project Sponsors

National Institutes of Health, UNM comprehensive cancer center, Environmental Health and Toxicology Pilot Awards from UNM Center for Native Environmental Health Equity Research and New Mexico Integrative Science Program Incorporating Research in Environmental Sciences, Cardiovascular and Metabolic Disease Research Program Pilot Project Grant from UNM HSC Office of Research Signature Programs

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