bims-imesem 2026-07-26 papers

Issue of 2026–07–26
five papers selected by
Akshara Kulkarni, University of Cambridge

Front Cell Infect Microbiol. 2026 ;16 1790475

Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.

Zhengqi Liang, Simiao Xing, Yujia Chen, Miaoxin Liu, Suhua Chang, Yuchen Cai, Qing Xiong, Yao Xu, Jinbiao Liu.

Due to their high mutation rates and adaptability, RNA viruses pose a persistent threat to public health. Cholesterol-25-hydroxylase (CH25H), an interferon-stimulated gene (ISG), produces 25-hydroxycholesterol (25HC), which plays a pivotal role in host defense against RNA virus infections. However, infection outcomes are determined by the dynamic interplay between viral infection and host immune defense, including cholesterol metabolism mediated by CH25H/25HC axis. This review aims to comprehensively elucidate the mechanisms underlying the interaction between CH25H/25HC and RNA viruses. We summarize recent advances in understanding the antiviral mechanisms of CH25H/25HC against RNA viruses, highlighting the central role of CH25H and its metabolite 25HC in inhibiting viral replication and regulating immune cell function. Furthermore, we discuss how RNA viruses evade host immune surveillance through strategies such as gene mutation, suppression of immune pathways, and interference with CH25H expression or function. Moreover, we emphasize endolysosomal cholesterol homeostasis as a host determinant of RNA virus entry, endosomal escape, trafficking, and replication, and discuss cholesterol-modulating host-directed therapies as complementary strategies to direct-acting antivirals. The findings indicate that dynamic regulation of CH25H and its metabolite 25HC is crucial for maintaining a balanced innate immune response against RNA viruses. This review comprehensively elucidated the dynamic molecular interactions between CH25H and RNA viruses, integrating recent research advances with a focus on molecular regulatory mechanisms. By synthesizing these findings, this review provided a mechanistic framework for understanding host-virus conflicts centered on cholesterol metabolism and proposed potential therapeutic strategies targeting this axis.

Keywords: CH25H; RNA virus evasion; antiviral response; cholesterol; lipid metabolism; regulatory mechanisms

DOI: https://doi.org/10.3389/fcimb.2026.1790475

iScience. 2026 Aug 21. 29(8): 116831

Mitochondrial dynamics and antiviral responses in Atlantic salmon cardiomyocytes during piscine myocarditis virus infection.

Antoni Malachowski, Deanna Lynn Wolfson, Randi Olsen, Alf Seljenes Dalum, Ida Sundvor Opstad, Krishna Agarwal, Roy Ambli Dalmo, Jaya Kumari Swain.

Viral infections in higher vertebrates are known to remodel mitochondrial dynamics, which play a critical role in regulating immune responses, energy production and cellular homeostasis. Currently, understanding of mitochondrial dynamics during viral infection in teleost is limited. This study provides the first detailed investigation of mitochondrial responses to piscine myocarditis virus (PMCV) infection, the causative agent of cardiomyopathy syndrome (CMS) and a severe cardiac disease in Atlantic salmon causing economic losses in aquaculture. This study investigates the temporal effects of PMCV infection in cardiomyocytes on mitochondrial dynamics, associated molecular responses using fluorescence microscopy, transmission electron microscopy, histopathology and RT-qPCR. Distinct mitochondrial subpopulations with specific morphologies and spatial distributions were identified. PMCV infection induced marked mitochondrial remodeling, characterized by early fission, followed by swelling and elongation at peak viral RNA levels. These findings link viral kinetics and immune response to mitochondrial remodeling, providing mechanistic insight into CMS pathogenesis and cardiac health.

Keywords: Atlantic salmon; CMS; PMCV; antiviral response; cardiomyocytes; cardiomyopathy syndrome; mitochondria; piscine myocarditis virus

DOI: https://doi.org/10.1016/j.isci.2026.116831

Front Immunol. 2026 ;17 1819389

Targeting macrophage metabolism: mechanisms, cellular crosstalk and implications in obesity-associated metabolic diseases.

Chensi Yao, Wei Zheng, Yamei Jin, Jiahao Sheng, Mengjiao Kang, Jijuan Zhong, Min Li, Liyun Duan, Xiao Yuan.

Obesity and its associated metabolic disorders constitute a prominent public health challenge. Diverse environmental and metabolic cues trigger alterations in macrophage metabolism, thereby influencing their functional phenotypes. Due to their phenotypic plasticity, macrophages play beneficial roles in tissue homeostasis, yet they also contribute to the progression of metabolic diseases. Consequently, beyond systemic chronic low-grade inflammation, greater attention should be directed toward immunometabolic dysfunction in metabolic tissues during obesity and its related diseases. This review summarizes the functional phenotypes and metabolic characteristics of macrophages, with an emphasis on how tissue niches influence macrophage function in the context of various obesity-related metabolic diseases. Enhanced understanding of the interplay between macrophages and metabolic target organs/tissues may provide novel therapeutic strategies for managing obesity and associated metabolic disorders.

Keywords: inflammation; macrophages; metabolism; obesity-associated metabolic diseases; polarization; reprogramming

DOI: https://doi.org/10.3389/fimmu.2026.1819389

MedComm (2020). 2026 Aug;7(8): e70868

Metabolic Regulation of Macrophages in Health and Disease.

Shan Huang, Yu Zhang, Jiali Min, Jiahui Yang, Yuchen Li, Hao Zhang, Shanshan Liu.

Macrophages orchestrate immune responses through remarkable phenotypic plasticity, which is intrinsically linked to their ability to reprogram intracellular metabolic pathways in response to microenvironmental cues. While recent advances have highlighted the role of aberrant macrophage metabolism in diverse diseases, a systematic synthesis integrating both intracellular and extracellular metabolic signals remains lacking. This review provides a comprehensive framework for understanding how core metabolic pathways-glycolysis, the TCA cycle, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and amino acid metabolism-are rewired during macrophage polarization under the orchestration of upstream signaling cascades, including NF-κB, PI3K/AKT/mTOR, JAK-STAT, and MAPK. We examine how exogenous metabolites such as succinate, itaconate, lactate, and amino acids reciprocally regulate macrophage function and discuss tissue-specific metabolic signatures of macrophage subsets-including alveolar macrophages （AMs), Kupffer cells (KCs), and tumor-associated macrophages (TAMs)-in the context of obesity, Type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), infections, autoimmune disorders, and cancer. We further evaluate emerging therapeutic strategies targeting macrophage metabolism, summarizing preclinical and clinical advances across signaling pathways, metabolic nodes, cytokines, and cell-based therapies with detailed trial data. By integrating cell-intrinsic metabolic circuitry with extracellular signals, this review establishes a theoretical foundation for metabolism-targeted immunotherapies and identifies key knowledge gaps for future investigation.

Keywords: immunometabolism; macrophage polarization; macrophages; metabolic diseases; metabolic regulation

DOI: https://doi.org/10.1002/mco2.70868

JCI Insight. 2026 Jul 21. pii: e204383. [Epub ahead of print]

Microbiome-Derived Metabolites Shape CD4⁺ T-Cell Differentiation and Immune Aging in HIV-1 Infection.

Amanda Cabral da Silva, Luke Flantzer, Jaclyn Weinberg, Shuya Kyu, Lisa P Daley-Bauer, Anyce Godoy, Ana Carolina Santana, Aarthi Talla, Amber Rittgers, Sarah Welbourn, David E Gordon, Jeffrey A Tomalka, Vincent C Marconi, Dean P Jones, Souheil-Antoine Younes.

The role of aromatic gut-derived bacterial metabolites (GDBMs) in shaping immune cell metabolism and function remains poorly explored. Using ex vivo metabolomic profiling of paired plasma and CD4⁺ T-cells from people living with HIV-1 (PLWH), we identified a network of aromatic GDBMs whose cell-associated abundance, rather than systemic levels, was linked to broad alterations in CD4⁺ T-cell metabolic and functional states. Among these, p-cresol sulfate (PCS) emerged as a mechanistic prototype. Ex vivo flow cytometry and single-cell RNA sequencing of CD4⁺ T-cells stratified by cell-associated PCS levels revealed dose-dependent enrichment of transcriptional programs associated with impaired differentiation, regulatory-like identity, and cellular senescence. In vitro transcriptomic and proteomic analyses of PCS-exposed CD4⁺ T cells demonstrated induction of cell-cycle arrest, mitochondrial dysfunction, and senescence-associated programs, including upregulation of p16 and p21. Integration of these immunometabolic findings with HIV-1 reservoir measurements revealed that CD4⁺ T-cell states defined by cell-associated GDBMs track with intact proviral DNA levels in vivo. These findings define a microbiome-derived axis that reshapes CD4⁺ T-cell metabolism and fate, promotes immune aging in PLWH, and may foster immunometabolic states linked to long-term HIV-1 reservoir persistence.

Keywords: AIDS/HIV; Adaptive immunity; Aging; Cellular senescence; Immunology; Metabolomics

DOI: https://doi.org/10.1172/jci.insight.204383