bims-ainimu 2026-02-22 papers

Issue of 2026–02–22
five papers selected by
Pedro Escoll Guerrero, Institut Pasteur

Nat Microbiol. 2026 Feb 20.

Gasdermins against intracellular bacterial pathogens.

Fernando W Souza, Yaxin Liu, Jacqueline Trujillo, Edward A Miao.

Intracellular bacterial pathogens can cause high levels of morbidity and mortality in humans. Host immune responses that protect against these infections include pyroptosis, a form of lytic cell death caused by the insertion of large gasdermin (GSDM) pores into the host plasma membrane. Here we review recent advances in our understanding of how the five GSDM proteins, GSDMA-E, are activated by distinct signalling pathways. Pyroptosis can both eliminate intracellular niches and release cytosolic interleukin-1 family cytokines that further prime host immune responses against the invading pathogen. Because pyroptosis targets microbes, host-adapted intracellular pathogens have evolved strategies to efficiently subvert it. However, environmental pathogens fail to evade, making pyroptosis a potent barrier against infection. We summarize recent findings for the host-adapted bacterial pathogens Shigella flexneri, Salmonella enterica serovar Typhimurium and Mycobacterium tuberculosis, contrasted with the environmental bacteria Burkholderia thailandensis and Chromobacterium violaceum.

DOI: https://doi.org/10.1038/s41564-026-02272-z

J Inflamm Res. 2026 ;19 562619

Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.

Mu Yuan, Lixing Tian, Xiang Xu.

Sepsis is a severe systemic inflammatory response syndrome, and macrophages play a crucial role in its pathogenesis. In recent years, more and more attention has been paid to the molecular signaling pathways of hypoxia, especially hypoxia-inducible factor 1-alpha (HIF-1α) and its related metabolic reprogramming, which have shown their importance in regulating the inflammatory response and functional state of macrophages. At present, although a large number of studies have explored the functional changes of macrophages in sepsis, there are still many unsolved mysteries about the specific mechanism and clinical significance of the effect of hypoxia signaling pathway on macrophage function and disease progression. In this review, the metabolic pathways regulated by HIF-1α, the activation of inflammasomes, the reprogramming of cell functions, and the effects of hypoxia-related signaling pathways on macrophage function and the pathological process of sepsis were summarized. Combined with the latest single-cell transcriptomics data and molecular mechanism research, we systematically explore the potential therapeutic targets and intervention strategies, which provide theoretical basis and research direction for the precise treatment of sepsis.

Keywords: HIF-1α; hypoxia; inflammasome; macrophages; metabolic reprogramming; sepsis; therapeutic target

DOI: https://doi.org/10.2147/JIR.S562619

Life Sci Alliance. 2026 May;pii: e202503333. [Epub ahead of print]9(5):

Glycolysis inhibition in tuberculosis-driven metabolic rewiring reduces HIV-1 spread in macrophages.

Tuberculosis (TB) is a significant aggravating factor in individuals living with HIV-1, the causative agent for AIDS. Both Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB, and HIV-1 target macrophages. Understanding how Mtb subverts these cells may facilitate the identification of new druggable targets. Here, we explored how TB can induce macrophages to form tunneling nanotubes (TNT), promoting HIV-1 spread. We found that TB triggers metabolic rewiring of macrophages, increasing their glycolytic ATP production. Using several pharmacological inhibitors, glucose deprivation, and glucose or galactose supplementation, we discovered that disrupting aerobic glycolysis significantly reduces HIV-1 infection in these macrophages. Glycolysis is essential for tunneling nanotubes formation, which facilitates viral transfer and cell-to-cell fusion. Importantly, HIF-1α activation contributes to these processes. Overall, these data might facilitate the development of targeted therapies aimed at inhibiting HIF-1α-dependent glycolytic activity in TB-induced immunomodulatory macrophages to ultimately halt HIV-1 dissemination in coinfected patients.

DOI: https://doi.org/10.26508/lsa.202503333

J Ethnopharmacol. 2026 Feb 14. pii: S0378-8741(26)00233-3. [Epub ahead of print]362 121382

Dihydromyricetin ameliorates Salmonella enteritidis-induced pyroptosis and intestinal damage in chickens via modulating NLRP3 inflammasome.

Desheng Wu, Xianan Fan, Zhenghua Ji, Xinru Jiang, Shibo Wang, Yani Ren, Changwen Li, Yicong Chang, Fangping Liu.

ETHNOPHARMACOLOGICAL RELEVANCE: Vine tea, as a non-camellia tea and ethnic medicine in China, exhibits an array of pharmacological effects. It exerts the effect of clearing heat and removing toxins, used to treat acute gastroenteritis, gastric ulcer, fever and hepatitis widely. Dihydromyricetin (DHM), abundant in vine tea, have been identified to have anti-inflammatory effect and antioxidant activity. Our prior research demonstrated that DHM mitigated intestinal damage induced by LPS in chickens. However, its potential mechanisms of action in Salmonella enteritidis (SE)-induced intestinal injury remain unclear.
AIM OF THE STUDY: To investigate whether DHM ameliorate intestinal function and cellular damage in chicken challenged by SE and further elucidate potential mechanisms.
MATERIALS AND METHODS: The metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Subsequently, network pharmacology was employed to predict the potential regulatory pathways of DHM against salmonella enteritis. Meanwhile, it was validated using Hy-Line white-feathered broiler and HD11 cells.
RESULTS: DHM significantly alleviated SE-induced intestinal pathological damage and serum metabolic disorders, reduced levels of pyroptosis-related factors LDH, IL-18 and IL-1β in chickens. Moreover, Network pharmacology analysis demonstrated that DHM might delay salmonella enteritis via pyroptosis by modulating inflammatory response and NOD-like receptor signaling pathway, with the NLRP3 inflammasome as a key target. Additionally, DHM reduced ROS levels and mitigated damage to cellular ultrastructure in SE-infected cells. Furthermore, DHM inhibited the activation of the NLRP3 inflammasome, thereby reducing the activation of caspase-1 and the expression of the pyroptosis effector protein GSDMA in vivo and in vitro.
CONCLUSIONS: DHM could ameliorate chicken serum metabolic disorders and inhibit pyroptosis and intestinal damage, possibly via modulating NLRP3 inflammasome.

Keywords: Dihydromyricetin; Metabolomics; NLRP3 inflammasome; Network pharmacology; Pyroptosis; Salmonella enteritidis

DOI: https://doi.org/10.1016/j.jep.2026.121382

Microb Pathog. 2026 Feb 12. pii: S0882-4010(26)00107-5. [Epub ahead of print]213 108381

The gut microbiota in Salmonella Typhi infection and translocation: Mechanisms of colonization resistance, pathogen subversion, and prospects for microecological intervention.

Chunyu Ma, Ziyi Zou, Wei Zhao, Yiwei Rao, Boheng Liu, Mengqi Sun, Dengyu Chen.

The systemic establishment of the strictly human-adapted pathogen Salmonella Typhi critically depends on functional interplay between its virulence effectors and the host gut microbiome. Organized within a "colonization-toxicity-immunity- microecological intervention" framework, this review synthesizes recent molecular and multi-omics evidence to delineate key host-pathogen-microbiota dynamics. During colonization, a healthy gut microbiota exerts multi-layered colonization resistance through nutrient and niche competition, as well as via microbial metabolites such as short-chain fatty acids and secondary bile acids. Current evidence more consistently supports DDR-associated cellular senescence and type I IFN signaling as major outcomes of typhoid toxin activity; pyroptosis, if observed, appears context-dependent and should not be presented as a universal endpoint. Concurrently, the Vi capsule and type III secretion system (T3SS) effector proteins (e.g., SteD) act in concert to disrupt innate and adaptive immunity, reprogram the mucosal immunometabolic landscape, and exacerbate microbial dysbiosis. We also evaluate the strength of evidence and applicability of microbiota-targeted interventions, including probiotics, prebiotics, synthetic microbial consortia, and fecal microbiota transplantation (FMT), and address the limitations of extrapolating from Salmonella Typhimurium mouse models to human Salmonella Typhi, typhoid toxin infection. Furthermore, we emphasize the need for cross-validation using human intestinal organoids, humanized immune mice, and population-level data, integrated with metabolomic and immune profiling, to establish a definitive "metabolism-immunity-toxicity" causal chain. Confronting the persistent evolution of H58 and other drug-resistant lineages, we propose a paradigm shift through the convergence of genomic epidemiology, microbiota-informed risk stratification, and vaccine-microbiota synergism; these elements collectively chart an implementable roadmap for precision medicine in disease control.

Keywords: Gut microbiota; Immune evasion; Microecological remodeling; Salmonella enterica serovar typhi; Salmonella typhi; Typhoid toxin