Key players in the regulation of iron homeostasis at the host-pathogen interface

Front Immunol. 2023 Oct 24:14:1279826. doi: 10.3389/fimmu.2023.1279826. eCollection 2023.

Abstract

Iron plays a crucial role in the biochemistry and development of nearly all living organisms. Iron starvation of pathogens during infection is a striking feature utilized by a host to quell infection. In mammals and some other animals, iron is essentially obtained from diet and recycled from erythrocytes. Free iron is cytotoxic and is readily available to invading pathogens. During infection, most pathogens utilize host iron for their survival. Therefore, to ensure limited free iron, the host's natural system denies this metal in a process termed nutritional immunity. In this fierce battle for iron, hosts win over some pathogens, but others have evolved mechanisms to overdrive the host barriers. Production of siderophores, heme iron thievery, and direct binding of transferrin and lactoferrin to bacterial receptors are some of the pathogens' successful strategies which are highlighted in this review. The intricate interplay between hosts and pathogens in iron alteration systems is crucial for understanding host defense mechanisms and pathogen virulence. This review aims to elucidate the current understanding of host and pathogen iron alteration systems and propose future research directions to enhance our knowledge in this field.

Keywords: hepatocytes; nutritional immunity; pathogens; siderophores; transferrin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Homeostasis
  • Iron* / metabolism
  • Mammals / metabolism
  • Siderophores* / metabolism
  • Transferrin / metabolism

Substances

  • Iron
  • Siderophores
  • Transferrin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Class B Breeding Program of Special Projects for Leading Science and Technology of the Chinese Academy of Sciences (XDPB16), the Fundamental Research Funds for the Central Universities, Beijing Municipal Natural Science Foundation (7202129), the National Natural Science Foundation of China (31571042), the Key Basic Research Project of Applied Basic Research Program of Hebei Province (18966315D), and One Hundred Outstanding Creative Talents Support Program of Hebei (BR2-218).