The Availability of Iron Is Involved in the Murine Experimental Toxoplasma gondii Infection Outcome.

Mário Cézar Oliveira,Loyane Bertagnolli Coutinho,Ester Cristina Borges Araujo,Neide Maria Silva,Marisol Pallete Briceño,Marcos Paulo Oliveira Almeida

doi:10.3390/microorganisms8040560

Mário Cézar Oliveira, Loyane Bertagnolli Coutinho + Show 4 more

Open Access

https://doi.org/10.3390/microorganisms8040560

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Journal: Microorganisms	Publication Date: Apr 14, 2020
Citations: 16	License type: CC BY 4.0

Affiliation: Universidade Federal de Uberlândia

Abstract

Iron is an important constituent of our environment, being necessary for both mammalian and pathogenic protozoa survival. Iron-containing proteins exert a wide range of biological processes such as biodegradation and biosynthesis, as well as immune function, fetal development, and physical and mental well-being. This work aimed to investigate the effect of iron deprivation in Toxoplasma gondii infection outcome. C57BL/6 mice were orally infected with T. gondii and treated with an iron chelator, deferoxamine, or supplemented with iron (ferrous sulfate), and the parasitism as well as immunological and histological parameters were analyzed. It was observed that the infection increased iron accumulation in the organs, as well as systemically, and deferoxamine treatment diminished the iron content in serum samples and intestine. The deferoxamine treatment decreased the parasitism and inflammatory alterations in the small intestine and lung. Additionally, they partially preserved the Paneth cells and decreased the intestinal dysbiosis. The ferrous sulfate supplementation, despite not significantly increasing the parasite load in the organs, increased the inflammatory alterations in the liver. Together, our results suggest that iron chelation, which is commonly used to treat iron overload, could be a promising medicine to control T. gondii proliferation, mainly in the small intestine, and consequently inflammation caused by infection.

Highlights

Iron is required as a functional component of many proteins in vertebrates, which are involved in a broad range of biochemical functions [1]
As the parasite load in the small intestine is higher after five days of infection [32], we investigated if T. gondii infection is able to induce iron accumulation in the small intestine as a necessity for its replication and proliferation on day 8 of parasite inoculation
It was observed that infected mice showed higher iron accumulation in the small intestine, lung, and liver (Figure 1B,D,F) on day 8 of parasite inoculation compared with non-infected mice (Figure 1A,C,E)

Summary

Introduction

Iron is required as a functional component of many proteins in vertebrates, which are involved in a broad range of biochemical functions [1]. Ferrous iron (Fe2+) is transported into the enterocytes mainly of the duodenum by the divalent metal ion transporter (DMT-1; formerly called DCT-1 or Nramp2), which is a member of the ‘natural-resistance-associated macrophage protein’ (Nramp) [3]. After transport into the enterocytes, ferrous iron can be used directly for intrinsic cellular metabolic processes (biosynthesis of heme), stored (intracellular ferritin), or exit the cell through the basolateral membrane transporter ferroportin (FPN1, or metal transporter protein 1 (MTP1) or iron-regulated transporter 1 (IREG1)), the mammalian cellular exporter of iron [4,5,6,7]. Ferroportin is localized on the surface of absorptive intestinal enterocytes, macrophages, hepatocytes, and placental cells, all of which release iron in plasma [4,5,6]. The extracellular iron is transported by transferrin (TF) and lactoferrin (LF) [8,9]

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