bims-toxgon 2024-05-05 papers

Immunohorizons. 2024 Apr 01. 8(4): 355-362

IL-12 Mediates T-bet-Expressing Myeloid Cell-Dependent Host Resistance against Toxoplasma gondii.

Madison L Schanz, Abigail M Bitters, Kamryn E Zadeii, Dana Joulani, Angela K Chamberlain, Américo H López-Yglesias.

To defend against intracellular pathogens such as Toxoplasma gondii, the host generates a robust type 1 immune response. Specifically, host defense against T. gondii is defined by an IL-12-dependent IFN-γ response that is critical for host resistance. Previously, we demonstrated that host resistance is mediated by T-bet-dependent ILC-derived IFN-γ by maintaining IRF8+ conventional type 1 dendritic cells during parasitic infection. Therefore, we hypothesized that innate lymphoid cells are indispensable for host survival. Surprisingly, we observed that T-bet-deficient mice succumb to infection quicker than do mice lacking lymphocytes, suggesting an unknown T-bet-dependent-mediated host defense pathway. Analysis of parasite-mediated inflammatory myeloid cells revealed a novel subpopulation of T-bet+ myeloid cells (TMCs). Our results reveal that TMCs have the largest intracellular parasite burden compared with other professional phagocytes, suggesting they are associated with active killing of T. gondii. Mechanistically, we established that IL-12 is necessary for the induction of inflammatory TMCs during infection and these cells are linked to a role in host survival.

DOI: https://doi.org/10.4049/immunohorizons.2400029

Curr Opin Microbiol. 2024 Apr 29. pii: S1369-5274(24)00060-2. [Epub ahead of print]79 102484

Time to switch gears: how long noncoding RNAs function as epigenetic regulators in Apicomplexan parasites.

Vera Mitesser, Karina Simantov, Ron Dzikowski.

Long noncoding RNAs (lncRNA) are emerging as important regulators of gene expression in eukaryotes. In recent years, a large repertoire of lncRNA were discovered in Apicomplexan parasites and were implicated in several mechanisms of gene expression, including marking genes for activation, contributing to the formation of subnuclear compartments and organization, regulating the deposition of epigenetic modifications, influencing chromatin and chromosomal structure and manipulating host gene expression. Here, we aim to update recent knowledge on the role of lncRNAs as regulators in Apicomplexan parasites and highlight the possible molecular mechanisms by which they function. We hope that some of the hypotheses raised here will contribute to further investigation and lead to new mechanistic insight and better understanding of the role of lncRNA in parasite's biology.

DOI: https://doi.org/10.1016/j.mib.2024.102484

PLoS One. 2024 ;19(5): e0303453

Correction: Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection.

Kousuke Umeda, Sachi Tanaka, Fumiaki Ihara, Junya Yamagishi, Yutaka Suzuki, Yoshifumi Nishikawa.

[This corrects the article DOI: 10.1371/journal.pone.0187703.].

DOI: https://doi.org/10.1371/journal.pone.0303453

Annu Rev Microbiol. 2024 Apr 29.

Inside the Host: Understanding the Evolutionary Trajectories of Intracellular Parasitism.

Pavla Bartošová-Sojková, Anzhelika Butenko, Jitka Richtová, Ivan Fiala, Miroslav Oborník, Julius Lukeš.

This review explores the origins of intracellular parasitism, an intriguing facet of symbiosis, where one organism harms its host, potentially becoming deadly. We focus on three distantly related groups of single-celled eukaryotes, namely Kinetoplastea, Holomycota, and Apicomplexa, which contain multiple species-rich lineages of intracellular parasites. Using comparative analysis of morphological, physiological, and molecular features of kinetoplastids, microsporidians, and sporozoans, as well as their closest free-living relatives, we reveal the evolutionary trajectories and adaptations that enabled the transition to intracellular parasitism. Intracellular parasites have evolved various efficient mechanisms for host acquisition and exploitation, allowing them to thrive in a variety of hosts. Each group has developed unique features related to the parasitic lifestyle, involving dedicated protein families associated with host cell invasion, survival, and exit. Indeed, parallel evolution has led to distinct lineages of intracellular parasites employing diverse traits and approaches to achieve similar outcomes.

DOI: https://doi.org/10.1146/annurev-micro-041222-025305

Curr Opin Microbiol. 2024 Apr 27. pii: S1369-5274(24)00029-8. [Epub ahead of print]79 102453

PII-like signaling proteins: a new paradigm in orchestrating cellular homeostasis.

Khaled A Selim, Vikram Alva.

Members of the PII superfamily are versatile, multitasking signaling proteins ubiquitously found in all domains of life. They adeptly monitor and synchronize the cell's carbon, nitrogen, energy, redox, and diurnal states, primarily by binding interdependently to adenyl-nucleotides, including charged nucleotides (ATP, ADP, and AMP) and second messengers such as Cyclic adenosine monophosphate, Cyclic di-adenosine monophosphate, and S-adenosylmethionine-AMP (SAM-AMP). These proteins also undergo a variety of posttranslational modifications, such as phosphorylation, adenylation, uridylation, carboxylation, and disulfide bond formation, which further provide cues on the metabolic state of the cell. Serving as precise metabolic sensors, PII superfamily proteins transmit this information to diverse cellular targets, establishing dynamic regulatory assemblies that fine-tune cellular homeostasis. Recently discovered, PII-like proteins are emerging families of signaling proteins that, while related to canonical PII proteins, have evolved to fulfill a diverse range of cellular functions, many of which remain elusive. In this review, we focus on the evolution of PII-like proteins and summarize the molecular mechanisms governing the assembly dynamics of PII complexes, with a special emphasis on the PII-like protein SbtB.

DOI: https://doi.org/10.1016/j.mib.2024.102453

J Transl Med. 2024 May 03. 22(1): 418

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.

Mengchen Xu, Yiming Hou, Na Li, Wenqian Yu, Lei Chen.

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.

Keywords: Epigenetic therapy; Head and neck squamous cell carcinoma; Histone deacetylases; Mechanism

DOI: https://doi.org/10.1186/s12967-024-05169-9

Vavilovskii Zhurnal Genet Selektsii. 2024 Apr;28(2): 215-227

Role of sirtuins in epigenetic regulation and aging control.

E M Samoilova, S E Romanov, D A Chudakova, P P Laktionov.

Advances in modern healthcare in developed countries make it possible to extend the human lifespan, which is why maintaining active longevity is becoming increasingly important. After the sirtuin (SIRT) protein family was discovered, it started to be considered as a significant regulator of the physiological processes associated with aging. SIRT has deacetylase, deacylase, and ADP-ribosyltransferase activity and modifies a variety of protein substrates, including chromatin components and regulatory proteins. This multifactorial regulatory system affects many processes: cellular metabolism, mitochondrial functions, epigenetic regulation, DNA repair and more. As is expected, the activity of sirtuin proteins affects the manifestation of classic signs of aging in the body, such as cellular senescence, metabolic disorders, mitochondrial dysfunction, genomic instability, and the disruption of epigenetic regulation. Changes in the SIRT activity in human cells can also be considered a marker of aging and are involved in the genesis of various age-dependent disorders. Additionally, experimental data obtained in animal models, as well as data from population genomic studies, suggest a SIRT effect on life expectancy. At the same time, the diversity of sirtuin functions and biochemical substrates makes it extremely complicated to identify cause-and-effect relationships and the direct role of SIRT in controlling the functional state of the body. However, the SIRT influence on the epigenetic regulation of gene expression during the aging process and the development of disorders is one of the most important aspects of maintaining the homeostasis of organs and tissues. The presented review centers on the diversity of SIRT in humans and model animals. In addition to a brief description of the main SIRT enzymatic and biological activity, the review discusses its role in the epigenetic regulation of chromatin structure, including the context of the development of genome instability associated with aging. Studies on the functional connection between SIRT and longevity, as well as its effect on pathological processes associated with aging, such as chronic inflammation, fibrosis, and neuroinflammation, have been critically analyzed.

Keywords: protein deacetylation; aging; epigenetic regulation; sirtuins

DOI: https://doi.org/10.18699/vjgb-24-26

Mol Cell. 2024 May 02. pii: S1097-2765(24)00131-X. [Epub ahead of print]84(9): 1816

Energy sensor AMPK gamma regulates translation via phosphatase PPP6C independent of AMPK alpha.

DOI: https://doi.org/10.1016/j.molcel.2024.02.012

Mol Cell. 2024 May 02. pii: S1097-2765(24)00139-4. [Epub ahead of print]84(9): 1629-1630

Response to: Energy sensor AMPKγ does not exist in isolation from AMPKα or interact with PPP6C in muscle and liver from humans and mice.

Qi Zhou, Xiaolei Cao, Bin Zhao.

DOI: https://doi.org/10.1016/j.molcel.2024.02.020