bims-traimu 2025-02-23 papers

Issue of 2025–02–23
five papers selected by
Yantong Wan, Southern Medical University

MicroPubl Biol. 2025 ;2025

PBMC and fibroblast cocultures to mimic the in vivo effect of BCG on trained immunity.

BCG greatly stimulates innate immune cells. Previous studies demonstrated that BCG-stimulated monocytes develop trained immunity whereby they respond to homologous and heterologous antigens. Previous studies used isolated monocytes or animal models to study BCG-induced trained immunity, which have benefits and limitations. To approximate in vivo conditions, we stimulated peripheral blood mononuclear cells (PBMCs) with BCG-treated human fibroblasts. We found that compared with BCG stimulation, the addition of fibroblasts increased the expression of IFN-γ in NK and γδ T cells and of TNF-α and IL-10 in monocytes. We conclude that BCG-treated fibroblasts offer advantages over BCG alone for studying trained immunity.

DOI: https://doi.org/10.17912/micropub.biology.001449

Vaccine. 2025 Feb 15. pii: S0264-410X(25)00181-1. [Epub ahead of print]51 126884

Non-specific effects of vaccines: The status and the future.

Christine Stabell Benn.

DOI: https://doi.org/10.1016/j.vaccine.2025.126884

Nat Metab. 2025 Feb 19.

Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation.

Alva M Casey, Dylan G Ryan, Hiran A Prag, Suvagata Roy Chowdhury, Eloïse Marques, Keira Turner, Anja V Gruszczyk, Ming Yang, Dane M Wolf, Jan Lj Miljkovic, Joyce Valadares, Patrick F Chinnery, Richard C Hartley, Christian Frezza, Julien Prudent, Michael P Murphy.

Macrophages stimulated by lipopolysaccharide (LPS) generate mitochondria-derived reactive oxygen species (mtROS) that act as antimicrobial agents and redox signals; however, the mechanism of LPS-induced mitochondrial superoxide generation is unknown. Here we show that LPS-stimulated bone-marrow-derived macrophages produce superoxide by reverse electron transport (RET) at complex I of the electron transport chain. Using chemical biology and genetic approaches, we demonstrate that superoxide production is driven by LPS-induced metabolic reprogramming, which increases the proton motive force (∆p), primarily as elevated mitochondrial membrane potential (Δψm) and maintains a reduced CoQ pool. The key metabolic changes are repurposing of ATP production from oxidative phosphorylation to glycolysis, which reduces reliance on F1FO-ATP synthase activity resulting in a higher ∆p, while oxidation of succinate sustains a reduced CoQ pool. Furthermore, the production of mtROS by RET regulates IL-1β release during NLRP3 inflammasome activation. Thus, we demonstrate that ROS generated by RET is an important mitochondria-derived signal that regulates macrophage cytokine production.

DOI: https://doi.org/10.1038/s42255-025-01224-x

Cell Mol Immunol. 2025 Feb 17.

Antigen-presenting innate lymphoid cells induced by BCG vaccination promote a respiratory antiviral immune response through the skin‒lung axis.

Dou Yu, Xintong Gao, Fei Shao, Zhen Liu, Aoyi Liu, Min Zhao, Zhuozhou Tang, Yude Guan, Shuo Wang.

The route of vaccine administration is associated with various immune outcomes, and the relationship between the route of administration and broad protection against heterologous pathogens remains unclear. Here, we found that subcutaneous vaccination with Bacillus Calmette-Guérin (BCG) promotes respiratory influenza clearance and T-cell responses. Group 1 innate lymphoid cells (ILC1s) express MHCII molecules and engage in antigen processing and presentation after BCG vaccination. During influenza virus infection, ILC1s in the lungs of BCG-vaccinated mice can present influenza virus antigens and prime Th1 cells. After subcutaneous vaccination with BCG, MHCII+ ILC1s migrate from the skin to the lungs and play an antigen-presenting role in influenza infection. Both the BCG and the BCG component lipomannan can induce MHCII expression and skin-to-lung migration of ILC1s via TLR2 signaling. Our study revealed an important regulatory mechanism by which subcutaneous vaccination with BCG promotes respiratory antiviral immune responses via the skin‒lung axis.

Keywords: Antigen-presenting innate lymphoid cells; Bacillus Calmette-Guérin; CD4+ T cells; respiratory virus infection; skin‒lung axis

DOI: https://doi.org/10.1038/s41423-025-01267-w

Cell Rep. 2025 Feb 13. pii: S2211-1247(25)00081-6. [Epub ahead of print]44(2): 115310

Lipid droplet efferocytosis attenuates proinflammatory signaling in macrophages via TREM2- and MS4A7-dependent mechanisms.

Linkang Zhou, You Lu, Xiaoxue Qiu, Zhimin Chen, Yuwei Tang, Ziyi Meng, Cong Yan, Hong Du, Siming Li, Jiandie D Lin.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by injury to steatotic hepatocytes that triggers the release of endogenous danger-associated molecular patterns. Recent work demonstrated that exposed lipid droplets (LDs) serve as a pathogenic signal that promotes monocyte infiltration and its maturation into triggering receptor expressed in myeloid cells 2 (TREM2+) macrophages in MASH liver. Here we explore the role of LD exposure in modulating inflammatory signaling in macrophages. We found that LD efferocytosis triggers a global transcriptional response and dampens pro-inflammatory signaling in macrophages. LD treatment attenuated NLRP3 inflammasome activation via mechanisms independent of lysosomal LD hydrolysis. While TREM2 was dispensable for LD efferocytosis by macrophages, it was required for the attenuation of proinflammatory signaling upon LD exposure. Additionally, MS4A7 downregulation contributes to LD efferocytosis-mediated dampening of inflammatory response. These results underscore the dual role of LD exposure in MASH liver by promoting monocyte infiltration and TREM2+ macrophage induction, while restraining proinflammatory response in macrophages.

Keywords: CP: Immunology; CP: Metabolism; MS4A7; NLRP3 inflammasome; TREM2; efferocytosis; inflammatory response; lipid droplets; macrophages

DOI: https://doi.org/10.1016/j.celrep.2025.115310