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

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.

Beneficial effects of Strongyloides venezuelensis antigen extract in acute experimental toxoplasmosis

“…Therefore, the reduced parasite load along with the increased survival observed in mice treated with S venezuelensis antigen reinforces its protective effect in T gondii infection. In advance, our group and others have shown that C57BL/6 mice present an intense inflammatory infiltration in peripheral organs 76,77 even in low doses of parasite inoculum 73,78‐80 . Thus, it was verified if the SvAg treatment could improve the inflammatory alterations induced by the parasite.…”

The ethanolic extract of the fungus Trichoderma stromaticum decreases the Toxoplasma gondii replication in vitro and ameliorates the experimental toxoplasmosis in vivo

“…The inflammatory score of the small intestine was represented as arbitrary units: 0–2, mild; 2–4, moderate; 4–6, severe; and above 6, very severe and was evaluated in the entire section, as previously described ( Oliveira et al., 2020 ). In the lung, the alveolar septa were measured in 10 microscopic fields using the ImageJ software version 1.50i and the inflammatory foci in the liver were quantified in 20 microscopic fields.…”

Orchestrating a heist: uptake and storage of metals by apicomplexan parasites

“…As obligate intracellular pathogens, any iron must be subverted from the host, but a conserved host defence is to limit available iron, known as nutritional immunity. These interactions are important as iron availability is often a key determinant of infection outcome [23,25,28]. There are two main options for the Apicomplexa to acquire host iron: the parasites could take up and recycle host iron-containing proteins, or they could directly access the host labile iron pool (LIP), a pool of exchangeable iron only loosely bound to small molecules in the cytoplasm.…”

“…Plasmodium species also require iron in their mosquito host, and iron accumulation in the mosquito has been linked to mosquito infection susceptibility [21]. In T. gondii, iron has been shown to be important in parasite replication and pathogenesis in vitro and in vivo [22][23][24][25] although there have been no clinical studies. There has also been little work on the importance of iron to Cryptosporidium, although anaemia was not associated with Cryptosporidium prevalence in one trial [26].…”

“…In T . gondii , iron has been shown to be important in parasite replication and pathogenesis in vitro and i n vivo ( Almeida et al, 2019 ; Dimier and Bout, 1998 ; Mahmoud, 1999 ; Oliveira et al, 2020 ) although there have been no clinical studies. There has also been little work on the importance of iron to Cryptosporidium , although anaemia was not associated with Cryptosporidium prevalence in one trial ( Mengist et al, 2015 ).…”