bims-ainimu 2026-02-01 papers

Issue of 2026–02–01
two papers selected by
Pedro Escoll Guerrero, Institut Pasteur

Front Cell Infect Microbiol. 2025 ;15 1662444

Lactate and lactylation in macrophage polarization of sepsis.

Jian Sun, Min Zhang, Li Zhang, Xinyue Zhang, Jingxiao Zhang.

Sepsis, which is characterized by potentially fatal multiple organ dysfunction, is caused by an abnormal host response to a major infection. During sepsis, the pathogen stimulates the host to activate resistance mechanisms that enhance immune cells' oxygen consumption in inflammatory tissues and cells, and promote aerobic glycolysis. Lactate generated by aerobic glycolysis is an essential substrate for the tricarboxylic acid cycle and for post-translational modifications via histone lactylation and epigenetic regulation. It also serves as a signaling molecule that modulates macrophage polarization between pro- and anti-inflammatory phenotypes in response to inflammatory and metabolic signals in their local environment. The roles of lactate and lactylation modifications in cancer cell proliferation and invasion have been well studied and are now potential therapeutic targets for various malignancies. However, the roles of lactate and lactylation modification in sepsis remain unclear. This review focuses on lactate's regulatory mechanism and lactylation modification during macrophage polarization in sepsis, and investigates whether this regulation could be a potential therapeutic target for sepsis.

Keywords: lactate; lactylation; macrophage polarization; metabolic reprogramming; sepsis

DOI: https://doi.org/10.3389/fcimb.2025.1662444

Mediators Inflamm. 2026 ;2026 3168669

Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.

Xiangxin Liao, Yixun Wang, Zhaohui Zhang, Xingguang Qu, Gaosheng Zhou.

Characterized by its capacity to induce organ failure, sepsis constitutes a life-threatening pathological state with high incidence and mortality rates. Current treatments primarily focus on antimicrobial therapy and organ support, lacking direct interventions targeting the restoration of cellular or organelle function. Among these mechanisms, mitochondrial dysfunction and overactivation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome stand out as key pathological hallmarks. As a classic inflammasome, the NLRP3 inflammasome, upon activation, drives cellular pyroptosis and massive release of inflammatory mediators. Beyond their role as cellular energy generators, mitochondria participate in the modulation of inflammatory responses and oxidative stress control. Mitochondrial quality control (MQC) serves as a prerequisite for the orderly performance of mitochondrial physiological functions. Disruption of MQC invariably results in mitochondrial dysfunction, triggering liberation of mitochondrial reactive oxygen species (mtROS) along with mitochondrial damage-associated molecular patterns (mtDAMPs), which serve as direct triggers for NLRP3 inflammasome formation and stimulation. This process disrupts MQC, exacerbates mitochondrial dysfunction, and forms a mutually reinforcing "MQC imbalance-NLRP3 overactivation" vicious cycle that drives disease progression. This review aims to: (1) systematically elucidate the complex bidirectional regulatory mechanisms between the NLRP3 inflammasome and MQC in the context of sepsis, (2) summarize the latest research progress on targeted intervention strategies based on this vicious cycle, and (3) discuss the challenges in clinical translation and future directions of these strategies.

Keywords: NLRP3 inflammasome; mitochondrial dysfunction; mitochondrial quality control; sepsis; targets; treatment

DOI: https://doi.org/10.1155/mi/3168669