Intracellular Iron Accumulation Facilitates Mycobacterial Infection in Old Mouse Macrophages

ABSTRACT: Aging has a significant impact on the immune system, leading to a gradual decline in immune function and changes in the body's ability to respond to bacterial infections. Non-tuberculous mycobacteria (NTM), also known as atypical mycobacteria or environmental mycobacteria, are commonly found in soil, water, and various environmental sources. While many NTM species are considered opportunistic pathogens, some can cause significant infections, particularly in individuals with compromised immune systems, such as the elderly. When mycobacteria enter the body, macrophages are among the first immune cells to encounter them, and attempt to engulf mycobacteria through a process called phagocytosis. Some NTM species, including Mycobacterium avium (M.avium) can survive and replicate within macrophages. However, little is known about the interaction between NTM and macrophages in the elderly. In this study, we investigated the mouse bone marrow-derived macrophage (BMMs) response to M. avium serotype 4, one of the main NTM species in patients with pulmonary NTM diseases. Our results demonstrated that old mouse BMMs have an increased level of intracellular iron and are more susceptible to M. avium serotype 4 infection compared to young mouse BMMs. The whole-cell proteomic analysis indicated a dysregulated expression of iron homeostasis-associated proteins in old mouse BMMs regardless of mycobacterial infection. Deferoxamine, an iron chelator, significantly rescued mycobacterial killing and phagolysosome maturation in old mouse BMMs. Therefore, our data indicate that an intracellular iron overload improves NTM survival within macrophages, and suggest a potential application of iron chelating drugs as a host-directed therapy for pulmonary NTM infection in the elderly

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mycobacterium Avium Mycobacterium Tuberculosis Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Steven Hartson  

LAB HEAD: Yong Cheng

PROVIDER: PXD045821 | Pride | 2024-05-24

REPOSITORIES: Pride