Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection

Ferreira, Paula Tatiane Mutão; Oliveira, Ana Carolina Morais de; Sousa, Roberto Augusto Pereira; Gomes, Beatriz Quaresemin; Félix, Jhennifer Estevão; Silva, Rafaela José; Millian, Iliana Balga; Assunção, Thaís Soares Farnesi de; Teixeira, Samuel Cota; Gomes, Marcos de Lucca Moreira; Silva, Marcos; Barbosa, Bellisa Freitas; Rodrigues, Virmondés; Mineo, José Roberto; Oliveira, Carlo José Freire; Ferro, Eloísa Amália Vieira; Gomes, A. da S.

doi:10.1016/j.imbio.2023.152357

Cited by 6 publications

(5 citation statements)

References 56 publications

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“…In addition, BpLec after 24 h treatment controls parasite invasion and replication by up-regulating the expression of MIF and IL-6 ( Castanheira et al, 2015 ). MIF acts as an inflammatory stimulatory molecule that inhibits T. gondii proliferation and promotes macrophage phagocytosis ( Ferreira et al, 2023 ). T. gondii inhibits the phagocytic capacity of MOs and drives migration to promote self-propagation ( Ten Hoeve et al, 2022 ).…”

Section: Potential Biological Mechanism Of Venom Peptides Against ...mentioning

confidence: 99%

Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

Yang

Liu

et al. 2023

Front. Pharmacol.

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Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis.

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Section: Potential Biological Mechanism Of Venom Peptides Against ...mentioning

confidence: 99%

Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

Yang

Liu

et al. 2023

Front. Pharmacol.

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“…MIF promotes eosinophil [41] and neutrophil migration [42], and thereby contributes to accumulation of these cells leading to tissue damage and remodeling under inflammatory conditions. MIF was equally found to promote macrophage polarization towards classically activated M1 cells [43,44]. Accordingly, MIF inhibition diminishes M1 activation [45].…”

Section: Introductionmentioning

confidence: 97%

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Vámos,

Kálmán,

Sturm

et al. 2023

Antioxidants

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Macrophage polarization is highly involved in autoimmunity. M1 polarized macrophages drive inflammation and undergo metabolic reprogramming, involving downregulation of mitochondrial energy production and acceleration of glycolysis. Macrophage migration inhibitory factor (MIF), an enigmatic tautomerase (ketonase and enolase), was discovered to regulate M1 polarization. Here, we reveal that KRP-6, a potent and highly selective MIF ketonase inhibitor, reduces MIF-induced human blood eosinophil and neutrophil migration similarly to ISO-1, the most investigated tautomerase inhibitor. We equally discovered that KRP-6 prevents M1 macrophage polarization and reduces ROS production in IFN-γ-treated cells. During metabolic reprogramming, KRP-6 improved mitochondrial bioenergetics by ameliorating basal respiration, ATP production, coupling efficiency and maximal respiration in LPS+IFN-γ-treated cells. KRP-6 also reduced glycolytic flux in M1 macrophages. Moreover, the selective MIF ketonase inhibitor attenuated LPS+IFN-γ-induced downregulation of PARP-1 and PARP-2 mRNA expression. We conclude that KRP-6 represents a promising novel therapeutic compound for autoimmune diseases, which strongly involves M1 macrophage polarization.

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“…Like MIF, D-DT is involved in various biological processes, including inflammation, tumorigenesis, and cell survival. Both MIF and D-DT have been implicated in the pathogenesis of various diseases, including autoimmune diseases, cancer, and infectious diseases [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…CD74 acts as the primary receptor for MIF, whereas CXCR2 and CXCR4 act as secondary receptors. D-DT also binds to CD74 but with lower affinity than MIF [9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Role of CD74 and D-Dopachrome Tautomerase in COVID-19: Insights from Transcriptomic and Serum Analyses

Ralchev Ralchev,

Lyubenova Bradyanova,

Valerieva Doneva

et al. 2023

JCM

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The COVID-19 pandemic has posed a significant threat to public health worldwide. While some patients experience only mild symptoms or no symptoms at all, others develop severe illness, which can lead to death. The host immune response is believed to play a crucial role in determining disease severity. In this study, we investigated the involvement of CD74 and D-DT in COVID-19 patients with different disease severities, by employing an in silico analysis of a publicly available transcriptomic dataset and by measuring their serum levels by ELISA. Our results showed a significant increase in MIF levels in PBMCs from COVID-19 patients, as well as a significant increase in the D-DT levels in PBMCs. However, we observed no modulation in the serum levels of D-DT. We also observed a concordant reduction in the serum levels and PBMCs expression levels of CD74. Furthermore, we found a negative correlation between CD74 serum levels and IL-13. In conclusion, our study sheds light on the involvement of CD74 and D-DT in COVID-19, with potential implications for disease severity and treatment. Further studies are needed to fully elucidate the mechanisms underlying these observations and to explore the potential therapeutic value of targeting CD74 and IL-13 in COVID-19.

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Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection

Cited by 6 publications

References 56 publications

Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming

Exploring the Role of CD74 and D-Dopachrome Tautomerase in COVID-19: Insights from Transcriptomic and Serum Analyses

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