Article
Immunology
Hironori Bando, Yasuhiro Fukuda, Nina Watanabe, Jeje Temitope Olawale, Kentaro Kato
Summary: This study reveals that abnormal glutamine metabolism induced by both interferon-gamma stimulation and Toxoplasma gondii infection triggers cyst formation in human neuroblastoma cells. The findings suggest that glutamine starvation in host cells is an important trigger of T. gondii stage conversion in human neurons.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Min Chen, Pei Yang, Zixuan Xin, Jiating Chen, Weihao Zou, Lijuan Zhou, Lili Yang, Jiao Peng, Hongjuan Peng
Summary: Toxoplasma gondii is a pathogen causing toxoplasmosis and has similarities with immunotherapy for cancers. The knockout of GRA5 gene in T. gondii resulted in an avirulent strain that stimulated immune responses. ME49 & UDelta;gra5 vaccination provided protection against T. gondii infection and breast cancer by boosting anti-tumor responses. The vaccine upregulated Th1 cytokines and tumor-infiltrating T cells, and increased the number of immune cells in the spleen.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Melissa A. Sleda, Zhu-Hong Li, Ranjan Behera, Baihetiya Baierna, Catherine Li, Jomkwan Jumpathong, Satish R. Malwal, Makoto Kawamukai, Eric Oldfield, Silvia N. J. Moreno
Summary: This study investigates the synthesis of polyprenyl diphosphate in Toxoplasma gondii and identifies the enzyme TgCoq1 as a key player in this process. The growth of TgCoq1 mutants is impaired, but can be rescued by complementation with a homologous gene or a related enzyme. Additionally, a bisphosphonate is found to inhibit T. gondii growth, which can be reversed by supplementation with long-chain ubiquinone. Importantly, the bisphosphonate also protects mice against lethal T. gondii infection.
Article
Biochemistry & Molecular Biology
Pallabi Mitra, Abhijit S. Deshmukh, Chinmayee Choudhury
Summary: Intracellular pathogens like Toxoplasma gondii manipulate host cell survival and stress response by targeting molecular chaperones such as Heat shock proteins (Hsps), particularly Hsp70. This study demonstrates that the selective inhibitor PES disrupts Hsp70 function, leading to dysregulation of host autophagy and attenuation of T. gondii multiplication. Interestingly, PES targets not only host Hsp70 but also the parasite's Hsp70 homologue, highlighting the potential of dual targeting for therapeutic interventions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Benedito M. Dos Santos, Jude M. Przyborski, Celia R. S. Garcia
Summary: English Summary: The GPCR-like SR25 in Plasmodium falciparum, a species of apicomplexan parasites, is activated by a shift in potassium concentration, allowing the parasite to take advantage of its development by sensing different ionic concentrations in the external milieu. This pathway involves the activation of phospholipase C and an increase in cytosolic calcium. This report summarizes the role of potassium ions during parasite development based on available literature, contributing to our understanding of the cell cycle of Plasmodium spp.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biology
Olivia L. McGovern, Yolanda Rivera-Cuevas, Vern B. Carruthers
Summary: Research on endocytosis in protozoan parasites, including malaria parasites and Toxoplasma gondii, is still in early stages. Malaria parasites acquire nutrients by internalizing hemoglobin from infected red blood cells, while the active endocytic system of Toxoplasma gondii was recently discovered. Future studies will help uncover the molecular basis and biological significance of endocytosis in Toxoplasma gondii.
Article
Immunology
Minmin Wu, Ran An, Nan Zhou, Ying Chen, Haijian Cai, Qi Yan, Ru Wang, Qingli Luo, Li Yu, Lijian Chen, Jian Du
Summary: IFN-gamma-activated macrophages can inhibit the replication of Toxoplasma gondii less virulent strain and promote the localization of immunity-related GTPases and guanylate-binding proteins through interaction with host autophagy proteins, thus controlling the proliferation of parasites.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Min Chen, Lijie Yao, Lijuan Zhou, Pei Yang, Weihao Zou, Liqing Xu, Shengmin Li, Hongjuan Peng
Summary: TgROP18(I) inhibits type I interferon responses to facilitate parasitic replication in various host cells.
Article
Chemistry, Medicinal
Kerrick C. Rees, Zhicheng Dou, Daniel C. Whitehead
Summary: This study synthesized a library of oxadiazon derivatives and discovered that 7 of them exhibited potent inhibition of intracellular growth in T. gondii. Further experiments confirmed that the mode of action was through the inhibition of protoporphyrinogen oxidase. These compounds showed no detectable cytotoxicity against human cells. Therefore, oxadiazon derivatives may serve as an effective molecular scaffold for the treatment of T. gondii infections.
ACS INFECTIOUS DISEASES
(2022)
Review
Immunology
Ao Cheng, Huanan Zhang, Baike Chen, Shengyao Zheng, Hongyi Wang, Yijia Shi, Siyao You, Ming Li, Liping Jiang
Summary: Toxoplasma gondii infection is a severe global health threat. By promoting host cell autophagy or attenuating the inhibition of autophagic targeting, novel therapeutic strategies against T. gondii can be developed.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Ling Ma, Maria Papadopoulou, Martin Taton, Francesca Genco, Arnaud Marchant, Valeria Meroni, David Vermijlen
Summary: A major population of Vgamma 9V82 T cells in human adult blood are activated by phosphorylated prenyl metabolites in a TCR-dependent manner, while fetal Vgamma 9V82 T cells respond differently and do not possess a cytotoxic effector phenotype. In utero infection with Toxoplasma gondii triggers expansion of Vgamma 9V82 T cells in the fetus, resulting in the acquisition of effector functions following parasite infections. This suggests that the human fetus can develop immune responses involving public Vgamma 9V82 T cells early in gestation.
Article
Parasitology
Gihan M. Tawfeek, Iman F. Abou-El-Naga, Eman Mohamed Elsayed Hassan, Dina Sabry, Rasha Abdallah Meselhey, Salwa Sami Younis
Summary: In this study, exosomes isolated from T. gondii infected human hepatoblastoma cells were evaluated for their potential as an immunizing agent against murine chronic toxoplasmosis. The results showed that exosome-alum induced both humoral and mixed Th1/Th2 cellular immune responses, and significantly reduced the brain cyst burden after challenge infection.
Article
Multidisciplinary Sciences
Joy M. Zeng, Sanduni V. Hapuarachchi, Sarah H. Shafik, Rowena E. Martin, Kiaran Kirk, Giel G. van Dooren, Adele M. Lehane
Summary: This study found that all three FNT proteins of T. gondii are located on the cell membrane, with TgFNT1 making the largest contribution to l-lactate transport during the parasite lytic cycle. Genetic analysis showed that these three genes can be disrupted individually or together without affecting the parasite's proliferation cycle.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Mary-Louise Wilde, Ushma Ruparel, Theresa Klemm, V. Vern Lee, Dale J. Calleja, David Komander, Christopher J. Tonkin
Summary: The phylum Apicomplexa consists of several parasitic species that are medically and agriculturally important. Despite its crucial role in eukaryotic biology, the ubiquitination machinery in apicomplexan parasites remains largely uncharacterized. Bioinformatic analysis of this machinery in apicomplexan parasites identified an expanded family of ovarian tumour domain-containing (OTU) deubiquitinase (DUB) enzymes in Toxoplasma, suggesting their functional significance. This study provides a comprehensive characterization of Toxoplasma OTU DUBs, including the identification of apicomplexan-specific enzymes. The biochemical analysis revealed their activity against various ubiquitin- and NEDD8-based substrates and their preferences for different types of ubiquitin linkages.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Heng Zhang, Xu Yang, Zhu Ying, Jing Liu, Qun Liu
Summary: DSK2b is a novel UBL-UBA shuttle protein that plays an important role in the degradation of ubiquitinated proteins and the synchronous cell division of T. gondii.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Diana J. Vaca, Gerhard Dobler, Silke F. Fischer, Christian Keller, Maik Konrad, Friederike D. von Loewenich, Sylvain Orenga, Siddhesh U. Sapre, Alex van Belkum, Volkhard A. J. Kempf
Summary: Many human infectious pathogens, especially zoonotic or vector-borne bacteria, are difficult to cultivate in laboratories due to their strong adaptation to their infected hosts. This hinders the diagnosis of diseases caused by these bacteria and the characterization of their resistance to antibiotics. This article describes the current state of microbiological diagnostics for five genera of fastidious bacteria, analyzing the limitations of current diagnostic protocols and exploring the potential of new technologies, such as mass spectrometry and next-generation nucleic acid sequencing, in improving diagnostic capabilities.
FEMS MICROBIOLOGY REVIEWS
(2022)
Article
Cell Biology
Nadine Gehrke, Marcus A. Woerns, Amrit Mann, Nadine Hoevelmeyer, Ari Waisman, Beate K. Straub, Peter R. Galle, Jorn M. Schattenberg
Summary: This study investigated the role of the Bcl-3 gene in acute liver failure (ALF). The results showed that overexpression of Bcl-3 protected against ALF by reducing liver damage, decreasing cell apoptosis and oxidative stress, and ultimately lowering the mortality rate.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Elisabeth M. Liebler-Tenorio, Johannes Heyl, Nadine Wedlich, Julia Figl, Heike Koehler, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Leander Grode, Stefan H. E. Kaufmann, Christian Menge
Summary: This study compares the development of tuberculous granulomas at the site of BCG vaccination and its recombinant derivatives in goats. The results show that granulomas with central caseous necrosis are induced by both BCG and its recombinant derivatives, although the size and extent of necrosis differ between vaccine strains. The recombinant derivatives induce fewer CD4(+) T and B cells and more CD8(+) cells in the granulomas compared to the parental BCG strain. Furthermore, the numbers of multinucleated giant cells (MNGCs) and cells with lipid bodies are significantly lower in groups administered with the recombinant BCG strains. These findings suggest that the granulomas induced by BCG and its recombinant derivatives in goats can serve as suitable models to compare reactions to different mycobacteria or tuberculosis vaccines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Giuseppe Locatelli, Filipa Marques-Ferreira, Antonis Katsoulas, Vasileia Kalaitzaki, Martin Krueger, Barbara Ingold-Heppner, Sabrina Walthert, Roman Sankowski, Olivia Prazeres da Costa, Amalia Dolga, Magdalena Huber, Maike Gold, Carsten Culmsee, Ari Waisman, Ingo Bechmann, Vladislava Milchevskaya, Marco Prinz, Achim Tresch, Burkhard Becher, Thorsten Buch
Summary: Research suggests that insulin-like growth factor 1 (IGF-1) signaling is not necessary for the function and survival of mature oligodendrocytes (ODCs) in the central nervous system (CNS). Lack of IGF-1 receptor in ODCs does not affect ODC survival and myelin status in toxin-induced and autoimmune demyelination models. Surprisingly, the absence of IGF-1 receptor in ODCs protects against clinical neuroinflammation in the autoimmune demyelination model.
Article
Multidisciplinary Sciences
Julia K. Prummer, Veronika M. Stein, Eliane Marti, Andreas Lutterotti, Ilijas Jelcic, Gertraud Schuepbach-Regula, Thorsten Buch, Arianna Maiolini
Summary: Meningoencephalitis of unknown origin (MUO) in dogs, similar to multiple sclerosis (MS) in humans, has a high prevalence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCBs) indicating an inflammatory B cell response.
Article
Allergy
Ragip Ertas, Murat Turk, Muhammed Burak Yucel, Melba Munoz, Sule Ketenci Ertas, Mustafa Atasoy, Marcus Maurer
Summary: The study found that eating can worsen the symptoms of symptomatic dermographism, while exercise can improve the condition, providing useful information for better symptom control in patients.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2023)
Review
Biology
Mirela Kristo, Liborija Lugovic-Mihic, Melba Munoz, Maja Rupnik, Aleksander Mahnic, Petar Ozretic, Morana Jaganjac, Diana Cesic, Matea Kuna
Summary: Recent studies have found a link between gut microorganism composition and chronic urticaria (CU), but the mechanisms underlying this connection are still unknown. The composition of the gut microbiome affects the immune system, so alterations in microbiota components could impact chronic spontaneous urticaria (CSU), including disease severity, patient quality of life, and treatment outcome. Studies have shown changes in gut microbiota composition in CSU patients, including a decrease in beneficial bacteria (Firmicutes and Bacteroides) and an increase in opportunistic bacteria (Enterobacteria and Proteobacteria). Abnormalities in unsaturated fatty acids and the butanoate metabolism pathway may also play a role in CSU. Understanding these findings could lead to improved clinical approaches and potential therapeutics for CSU patients.
Article
Biochemistry & Molecular Biology
Julia Figl, Heike Koehler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann, Christian Menge
Summary: A more effective vaccine against tuberculosis is urgently needed. The recombinant vaccine VPM1002 has been found to be safer and more efficacious than the existing vaccine BCG in mice models. In this study, the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, were assessed in juvenile goats. The results showed that VPM1002 and NUOG induced anti-tuberculous immunity with a comparable safety profile to BCG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Yana Hackler, Frank Siebenhaar, Marcus Maurer, Melba Munoz
Summary: This study found that mast cells can directly activate virus-specific CD8(+) T cells and promote their antiviral response during viral infections. Mast cells cluster with virus-specific CD8(+) T cells and induce their activation and production of antiviral cytokines through direct cellular interaction. This finding contributes to a better understanding of the antiviral functions of mast cells and may provide new strategies for treating viral infections.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Parasitology
Aparajita Lahree, Joao Mello-Vieira, Maria M. Mota
Summary: Malaria is a febrile illness caused by Plasmodium parasites, which infect erythrocytes and lead to clinical symptoms and pathology. Understanding the metabolism of liver-stage parasites is crucial for identifying cellular pathways essential for infection and developing treatments. This review provides a summary of current knowledge on nutrient acquisition and biosynthesis by liver-stage parasites, highlighting gaps in knowledge and challenges in this field.
TRENDS IN PARASITOLOGY
(2023)
Article
Neurosciences
Daniela C. C. Ivan, Kristina Carolin Berve, Sabrina Walthert, Gianni Monaco, Katharina Borst, Elisa Bouillet, Filipa Ferreira, Henry Lee, Jasmin Steudler, Thorsten Buch, Marco Prinz, Britta Engelhardt, Giuseppe Locatelli
Summary: Signaling by insulin-like growth factor-1 (IGF-1) is crucial for the development and survival of the CNS. However, its role in microglia/macrophages and neuroinflammation is still unclear, resulting in contradictory reports on its therapeutic potential for diseases like MS and EAE.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biology
Ines M. Marreiros, Sofia Marques, Ana Parreira, Vincent Mastrodomenico, Bryan C. Mounce, Chantal T. Harris, Bjoern F. Kafsack, Oliver Billker, Vanessa Zuzarte-Luis, Maria M. Mota
Summary: Plasmodium parasites rely on an efficient sensing pathway to respond to amino acid fluctuations. The nek4, eIK1, and eIK2 sensor kinases play a key role in Plasmodium amino acid sensing, enabling these parasites to fine-tune replication and development in response to amino acid availability. This complex mechanism is critical for modulating parasite growth and survival.
COMMUNICATIONS BIOLOGY
(2023)
Article
Veterinary Sciences
Vladislava Milchevskaya, Philippe Bugnon, Emiel B. J. ten Buren, Dominique Vanhecke, Frank Brand, Achim Tresch, Thorsten Buch
Summary: Colony management of gene-modified animals is complicated and costly, influenced by random events and genetics. The authors developed an R package that optimizes breeding design and provides information about the optimal number of breedings, considering species-specific properties. The software also allows breeding planning for balanced male-to-female ratio or single-sex experiments.
Article
Veterinary Sciences
Peter Dobrowolski, Thorsten Buch, Stefan Nagel-Riedasch
Summary: Information on the diploid genotype of gene-modified or mutant laboratory animals is crucial for breeding and experimental planning, as well as for animal exchange and communication with genotyping service providers. Standardized nomenclature for representing the diploid genotype is needed, and the proposed recommendations provide a practical and standardized guide for animal care and scientific personnel in research facilities.
LABORATORY ANIMALS
(2023)
Article
Neurosciences
Monica M. Santisteban, Samantha Schaeffer, Antoine Anfray, Giuseppe Faraco, David Brea, Gang Wang, Melissa J. Sobanko, Rose Sciortino, Gianfranco Racchumi, Ari Waisman, Laibaik Park, Josef Anrather, Costantino Iadecola
Summary: This study reveals the critical role of meningeal T cells and macrophage IL-17 signaling in the neurovascular and cognitive dysfunction in a mouse model of hypertension.
NATURE NEUROSCIENCE
(2023)