Complex Interaction of Deferasirox and Pythium insidiosum: Iron-Dependent Attenuation of Growth In Vitro and Immunotherapy-Like Enhancement of Immune Responses In Vivo

Zanette, Régis A.; Bitencourt, Paula Eliete Rodrigues; Kontoyiannis, Dimitrios P.; Fighera, Rafael A.; Flores, Mariana M.; Kommers, Gláucia D.; Silva, Priscila S.; Ludwig, Aline; Moretto, Maria Beatriz; Alves, Sydney Hartz; Santurio, Jânio M.

doi:10.1371/journal.pone.0118932

Cited by 10 publications

(11 citation statements)

References 21 publications

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“…1B). Indeed, this "nutritional immunity" became apparent in the 1940s for animals, including humans, and is now wellestablished (92)(93)(94). For example, the mammalian hormone hepcidin is deployed to block iron transport and retain intracellular iron pools, particularly in macrophages (95).…”

Section: Mechanisms Through Which Plants Interfere With Pathogen Ironmentioning

confidence: 99%

Iron homeostasis and plant immune responses: Recent insights and translational implications

Herlihy

Long

McDowell

2020

Journal of Biological Chemistry

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Iron (Fe) metabolism and the plant immune system are both critical for plant vigor in natural ecosystems and for reliable agricultural productivity. Mechanistic studies of plant iron homeostasis and plant immunity have traditionally been carried out in isolation from each other; however, our growing understanding of both processes has uncovered significant connections. For example, iron plays a critical role in the generation of reactive oxygen intermediates during immunity and has been recently implicated as a critical factor for immune-initiated cell death via ferroptosis. Moreover, plant iron stress triggers immune activation, suggesting that sensing of iron depletion is a mechanism by which plants recognize a pathogen threat. The iron deficiency response engages hormone signaling sectors that are also utilized for plant immune signaling, providing a probable explanation for iron-immunity cross-talk. Finally, interference with iron acquisition by pathogens might be a critical component of the immune response. Efforts to address the global burden of iron deficiency-related anemia, have focused on classical breeding and transgenic approaches to develop crops biofortified for iron content. However, our improved mechanistic understanding of plant iron metabolism suggests that such alterations could promote or impede plant immunity, depending on the nature of the alteration and the virulence strategy of the pathogen. Effects of iron biofortification on disease resistance should be evaluated while developing plants for iron biofortification.

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Section: Mechanisms Through Which Plants Interfere With Pathogen Ironmentioning

confidence: 99%

Iron homeostasis and plant immune responses: Recent insights and translational implications

Herlihy

Long

McDowell

2020

Journal of Biological Chemistry

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“…Iron chelation augments tumor necrosis factor alpha (TNF-α), GM-CSF and IFN-γ release from monocytes/macrophages in thalassemia patients irrespective of ferritin levels (Ud-Naen et al, 2019). In vitro data showed that deferasirox directly damages P. insidiosum hyphae (Zanette et al, 2015). In the rabbit model of pythiosis, deferasirox exhibits an immuno-modulating effect which is similar to that of the immunotherapy (Zanette et al, 2015).…”

Section: Iron Chelatorsmentioning

confidence: 98%

“…In vitro data showed that deferasirox directly damages P. insidiosum hyphae (Zanette et al, 2015). In the rabbit model of pythiosis, deferasirox exhibits an immuno-modulating effect which is similar to that of the immunotherapy (Zanette et al, 2015). Clinically, various iron chelators, i.e., deferiprone, deferasirox, and deferoxamine have been used adjunctively in thalassemia patients to treat iron overload (Permpalung et al, 2015;Worasilchai et al, 2018).…”

Section: Iron Chelatorsmentioning

confidence: 99%

Recent update in diagnosis and treatment of human pythiosis

Chitasombat

Jongkhajornpong

Lekhanont

et al. 2020

PeerJ

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Human pythiosis is an infectious condition with high morbidity and mortality. The causative agent is the oomycete microorganism Pythium insidiosum. The pathogen inhabits ubiquitously in a wet environment, and direct exposure to the pathogen initiates the infection. Most patients with pythiosis require surgical removal of the affected organ, and many patients die from the disease. Awareness of pythiosis among healthcare personnel is increasing. In this review, we summarized and updated information on the diagnosis and treatment of human pythiosis. Vascular and ocular pythiosis are common clinical manifestations. Recognition of the typical clinical features of pythiosis is essential for early diagnosis. The definitive diagnosis of the disease requires laboratory testing, such as microbiological, serological, molecular, and proteomic assays. In vascular pythiosis, surgical intervention to achieve the organism-free margin of the affected tissue, in combination with the use of antifungal drugs and P. insidiosum immunotherapy, remains the recommended treatment. Ocular pythiosis is a serious condition and earliest therapeutic penetrating keratoplasty with wide surgical margin is the mainstay treatment. Thorough clinical assessment is essential in all patients to evaluate the treatment response and detect an early sign of the disease recurrence. In conclusion, early diagnosis and proper management are the keys to an optimal outcome of the patients with pythiosis.

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“…It is therefore clear that, in these conditions, an iron chelation therapeutic strategy could potentially be of utmost relevance to trigger (or release) an efficient anti-tumor response in cancer patients. Indeed, iron chelating agents such as deferasirox, an oral iron chelator currently used for the treatment of iron overload, demonstrated the capability to increase the Th1 response and to increase CD8 lymphocyte count in animal models of infections [ 147 ]. Additionally, by reducing regulatory T cells and enhancing the NK response, deferasirox improved the outcome of patients affected by acute myeloid leukemia after allogeneic stem cell transplantation (i.e., promoted a graft-versus-leukemia response) [ 148 ].…”

Section: Iron In Time As New Target For Oncotherapymentioning

confidence: 99%

Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

Sacco

Battaglia

Botta

et al. 2021

Cells

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New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.

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Complex Interaction of Deferasirox and Pythium insidiosum: Iron-Dependent Attenuation of Growth In Vitro and Immunotherapy-Like Enhancement of Immune Responses In Vivo

Cited by 10 publications

References 21 publications

Iron homeostasis and plant immune responses: Recent insights and translational implications

Iron homeostasis and plant immune responses: Recent insights and translational implications

Recent update in diagnosis and treatment of human pythiosis

Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

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