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Immunogenic cell death (ICD) is a regulated cell death process distinguished by its ability to stimulate an adaptive immune response. This occurs through the emission of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), adenosine triphosphate (ATP), High Mobility Group Box 1 (HMGB1), type I interferons (IFN-α/β), and heat shock proteins(HSPs). Collectively, these signals promote dendritic cells (DCs) maturation, facilitate antigen cross-presentation, and trigger cytotoxic T lymphocytes (CTLs) activation. This cascade of immunostimulatory events is critical for converting immunologically “cold” tumors into “hot” ones. This review systematically explains the molecular mechanism of ICD, focusing on the space-time regulation of DAMPs emission and their role in remodeling the tumor immune environment. We also list a variety of ICD inducers, including conventional chemotherapeutic drugs, targeted drugs, nanotechnology-driven systems, physical means, and tumor-lytic viruses. The core theme is the synergistic potential of ICD with immune checkpoint inhibitors(ICIs), chimeric antigen receptor T cells (CAR-T cells)therapy, and microbiome regulation, supported by emerging preclinical and clinical evidence. We also discuss some current challenges, such as the heterogeneity of tumors released by DAMPs and immune escape mechanisms, and explore the development of biomarkers for patient stratification. In the future, we have emphasized some promising research directions, including artificial intelligence-assisted drug design, spatially differentiated metometric technology, and engineered immune cell therapy to achieve precise space-time-induced immune cell death. This review presents the mechanistic insights and transformative research directions for positioning ICD as a central pillar in the future landscape of immuno-oncology.

Mitochondria serve as a hub for a multitude of vital cellular processes. To ensure an efficient deployment of mitochondrial tasks, organelle homeostasis needs to be preserved. Mitochondrial quality control (MQC) mechanisms (i.e., mitochondrial dynamics, biogenesis, proteostasis, and autophagy) are in place to safeguard organelle integrity and functionality. Defective MQC has been reported in several conditions characterized by chronic low-grade inflammation. In this context, the displacement of mitochondrial components, including mitochondrial DNA (mtDNA), into the extracellular compartment is a possible factor eliciting an innate immune response. The presence of bacterial-like CpG islands in mtDNA makes this molecule recognized as a damaged-associated molecular pattern by the innate immune system. Following cell death-triggering stressors, mtDNA can be released from the cell and ignite inflammation via several pathways. Crosstalk between autophagy and apoptosis has emerged as a pivotal factor for the regulation of mtDNA release, cell’s fate, and inflammation. The repression of mtDNA-mediated interferon production, a powerful driver of immunological cell death, is also regulated by autophagy–apoptosis crosstalk. Interferon production during mtDNA-mediated inflammation may be exploited for the elimination of dying cells and their conversion into elements driving anti-tumor immunity.

[This corrects the article DOI: 10.3389/fphar.2023.1212771.].[This corrects the article DOI: 10.3389/fphar.2023.1212771.].

[This corrects the article DOI: 10.3389/fimmu.2022.886374.].[This corrects the article DOI: 10.3389/fimmu.2022.886374.].

Plants constantly monitor and cope with the fluctuating environment while hosting a diversity of plant-inhabiting microbes. The mode and outcome of plant–microbe interactions, including plant disease epidemics, are dynamically and profoundly influenced by abiotic factors, such as light, temperature, water and nutrients. Plants also utilize associations with beneficial microbes during adaptation to adverse conditions. Elucidation of the molecular bases for the plant–microbe–environment interactions is therefore of fundamental importance in the plant sciences. Following advances into individual stress signaling pathways, recent studies are beginning to reveal molecular intersections between biotic and abiotic stress responses and regulatory principles in combined stress responses. We outline mechanisms underlying environmental modulation of plant immunity and emerging roles for immune regulators in abiotic stress tolerance. Furthermore, we discuss how plants coordinate conflicting demands when exposed to combinations of different stresses, with attention to a possible determinant that links initial stress response to broad-spectrum stress tolerance or prioritization of specific stress tolerance.

Ischemic stroke is a major cause of death. Besides the direct damage resulting from oxygen and glucose deprivation, sterile inflammation plays a pivotal role in increasing cellular death. Damaged-associated molecular patterns (DAMPs) are passively released from dying cells and activate the innate immune system. Thus, they take part in the direct and rapid activation of the inflammatory response after stroke onset. In this review the role of the most important DAMPs, high mobility group box 1, heat and cold shock proteins, purines, and peroxiredoxins, are addressed. Moreover, intracellular pathways activated by DAMPs in microglia are illuminated.

Immunogenic cell death (ICD) is a form of cell death that can engage immunity. Therapeutic engagement of ICD in cancer may lead to more effective responses by eliciting antitumor immunity. Here, we discuss various modalities of ICD, highlighting our current understanding of the molecular basis of ICD. Finally, we outline the potential and challenge of harnessing ICD in cancer immunotherapy. Immunogenic cell death (ICD) is a type of cancer cell death triggered by certain chemotherapeutic drugs, oncolytic viruses, physicochemical therapies, photodynamic therapy, and radiotherapy. It involves the activation of the immune system against cancer in immunocompetent hosts. ICD comprises the release of damage‐associated molecular patterns (DAMPs) from dying tumor cells that result in the activation of tumor‐specific immune responses, thus eliciting long‐term efficacy of anticancer drugs by combining direct cancer cell killing and antitumor immunity. Remarkably, subcutaneous injection of dying tumor cells undergoing ICD has been shown to provoke anticancer vaccine effects in vivo. DAMPs include the cell surface exposure of calreticulin (CRT) and heat‐shock proteins (HSP70 and HSP90), extracellular release of adenosine triphosphate (ATP), high‐mobility group box‐1 (HMGB1), type I IFNs and members of the IL‐1 cytokine family. In this review, we discuss the cell death modalities connected to ICD, the DAMPs exposed during ICD, and the mechanism by which they activate the immune system. Finally, we discuss the therapeutic potential and challenges of harnessing ICD in cancer immunotherapy.

Pathogen-associated molecular patterns (PAMPs), microbe-associated molecular patterns (MAMPs), herbivore-associated molecular patterns (HAMPs), and damage-associated molecular patterns (DAMPs) are molecules produced by microorganisms and insects in the event of infection, microbial priming, and insect predation. These molecules are then recognized by receptor molecules on or within the plant, which activates the defense signaling pathways, resulting in plant’s ability to overcome pathogenic invasion, induce systemic resistance, and protect against insect predation and damage. These small molecular motifs are conserved in all organisms. Fungi, bacteria, and insects have their own specific molecular patterns that induce defenses in plants. Most of the molecular patterns are either present as part of the pathogen’s structure or exudates (in bacteria and fungi), or insect saliva and honeydew. Since biotic stresses such as pathogens and insects can impair crop yield and production, understanding the interaction between these organisms and the host via the elicitor–receptor interaction is essential to equip us with the knowledge necessary to design durable resistance in plants. In addition, it is also important to look into the role played by beneficial microbes and synthetic elicitors in activating plants’ defense and protection against disease and predation. This review addresses receptors, elicitors, and the receptor–elicitor interactions where these components in fungi, bacteria, and insects will be elaborated, giving special emphasis to the molecules, responses, and mechanisms at play, variations between organisms where applicable, and applications and prospects.

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability of digesting NET DNA scaffold. Moreover, recent advances in neutrophil biology led to the development of selective NET inhibitors, which also appear to reduce ALI in experimental models. Here we provide an overview of the role of NETs in different forms of ALI discussing existing gaps in our knowledge and novel therapeutic approaches to modulate their impact on lung injury.

Sepsis is a deadly inflammatory syndrome caused by an exaggerated immune response to infection. Much has been focused on host response to pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Some well described members of the DAMP family are extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), histones, and adenosine triphosphate (ATP). DAMPs are released from the cell through inflammasome activation or passively following cell death. Similarly, neutrophil extracellular traps (NETs) are released from neutrophils during inflammation. NETs are webs of extracellular DNA decorated with histones, myeloperoxidase, and elastase. Although NETs contribute to pathogen clearance, excessive NET formation promotes inflammation and tissue damage in sepsis. Here, we review DAMPs and NETs and their crosstalk in sepsis with respect to their sources, activation, release, and function. A clear grasp of DAMPs, NETs and their interaction is crucial for the understanding of the pathophysiology of sepsis and for the development of novel sepsis therapeutics.