Distinct Effects of Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus Cell Wall Component-Induced Inflammation on the Iron Metabolism of THP-1 Cells

Edina Pandur,Katalin Sipos,Kitti Tamási,Ramóna Pap,Gergely Jánosa

doi:10.3390/ijms22031497

Edina Pandur, Katalin Sipos + Show 3 more

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https://doi.org/10.3390/ijms22031497

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Abstract

Macrophages are essential immune cells of the innate immune system. They participate in the development and regulation of inflammation. Macrophages play a fundamental role in fighting against bacterial infections by phagocytosis of bacteria, and they also have a specific role in immunomodulation by secreting pro-inflammatory cytokines. In bacterial infection, macrophages decrease the serum iron concentration by removing iron from the blood, acting as one of the most important regulatory cells of iron homeostasis. We examined whether the Gram-positive and Gram-negative cell wall components from various bacterial strains affect the cytokine production and iron transport, storage and utilization of THP-1 monocytes in different ways. We found that S. aureus lipoteichoic acid (LTA) was less effective in activating pro-inflammatory cytokine expression that may related to its effect on fractalkine production. LTA-treated cells increased iron uptake through divalent metal transporter-1, but did not elevate the expression of cytosolic and mitochondrial iron storage proteins, suggesting that the cells maintained iron efflux via the ferroportin iron exporter. E. coli and P. aeruginosa lipopolysaccharides (LPSs) acted similarly on THP-1 cells, but the rates of the alterations of the examined proteins were different. E. coli LPS was more effective in increasing the pro-inflammatory cytokine production, meanwhile it caused less dramatic alterations in iron metabolism. P. aeruginosa LPS-treated cells produced a smaller amount of pro-inflammatory cytokines, but caused remarkable elevation of both cytosolic and mitochondrial iron storage proteins and intracellular iron content compared to E. coli LPS. These results prove that LPS molecules from different bacterial sources alter diverse molecular mechanisms in macrophages that prepossess the outcome of the bacterial infection.

Highlights

Macrophages are essential immune cells of the innate immune system [1]
We examined two different types of LPS obtained from E. coli and P. aeruginosa Gram-negative bacterial strains, and lipoteichoic acid (LTA) purified from the Gram-positive bacterium S. aureus to reveal the differences between their effects on pro-inflammatory cytokine (IL-1β, IL-6 and TNFα) production, on soluble FKN secretion and on the iron transport and storage of THP-1 human monocytes
Bacterial infections activate different Toll-like receptors (TLRs) on macrophages and regulate the expression of pro-inflammatory cytokines via the NFκB signaling pathway, but it seems that various bacterial strains may influence the production of inflammatory molecules differently [10,11]

Summary

Introduction

Macrophages are essential immune cells of the innate immune system [1]. They participate in the development and regulation of inflammation [2]. Gram-negative and Gram-positive bacteria activate the macrophages via Toll-like receptors (TLRs) [4]. The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) binds to TLR4, while the Gram-positive cell wall polymer lipoteichoic acid (LTA) activates TLR2 [5,6]. Both receptors activate the NFκB signaling pathway and the transcription of pro-inflammatory cytokines [7]. Surbatovic et al revealed that the cytokine profiles of patients with abdominal sepsis are different in the cases of

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