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Review
. 2015 Jul 31;290(31):18991-8.
doi: 10.1074/jbc.R115.645085. Epub 2015 Jun 8.

Nutritional Immunity: S100 Proteins at the Host-Pathogen Interface

Joseph P Zackular  1 , Walter J Chazin  2 , Eric P Skaar  3
Affiliations
Review

Nutritional Immunity: S100 Proteins at the Host-Pathogen Interface

Joseph P Zackular et al. J Biol Chem. .

Abstract

The S100 family of EF-hand calcium (Ca(2+))-binding proteins is essential for a wide range of cellular functions. During infection, certain S100 proteins act as damage-associated molecular patterns (DAMPs) and interact with pattern recognition receptors to modulate inflammatory responses. In addition, these inflammatory S100 proteins have potent antimicrobial properties and are essential components of the immune response to invading pathogens. In this review, we focus on S100 proteins that exhibit antimicrobial properties through the process of metal limitation, termed nutritional immunity, and discuss several recent advances in our understanding of S100 protein-mediated metal sequestration at the site of infection.

Keywords: S100 proteins; S100A12; S100A7; bacteria; calprotectin; host-pathogen interaction; immunology; microbiology; nutritional immunity.

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Figures

FIGURE 1.
FIGURE 1.
Structures of S100 proteins involved in nutritional immunity. A, structure of Zn2+-bound S100A7 homodimer (23). B, structure of Cu2+-bound S100A12 homodimer (55). C, structure of S100A8/S100A9 calprotectin heterodimer bound to Zn2+ in Site II and Mn2+ in Site I (12, 75).
FIGURE 2.
FIGURE 2.
Model of S100 protein-mediated metal sequestration and inflammatory response at the site of infection. S100 proteins are released into the extracellular milieu and compete for transition metals with pathogens at the site of infection. Due to their high affinity for transition metals, the transition metals essential to growth and survival are limited at the site of infection, and pathogens are cleared. During infection, S100 proteins stimulate the pro-inflammatory immune response through interaction with RAGE and TLR4. This leads to NF-κB-mediated inflammatory cascade and the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. This inflammatory response also leads to increased expression of S100 proteins and the start of a positive feedback loop. S100 proteins, such as calprotectin, can also act as reactive oxygen species scavengers and limit collateral damage to the host.
See this image and copyright information in PMC

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