The BH3-interacting domain death agonist (Bid), a proapoptotic signaling molecule of the B-cell lymphoma 2 (Bcl-2) family, is a key regulator of mitochondrial outer membrane (MOM) permeability. Uniquely positioned at the intersection of extrinsic and intrinsic apoptosis pathways, Bid links death receptor signaling to the mitochondria-dependent cascade and can also be activated by endoplasmic reticulum (ER) stress. In its active forms, cleaved Bid (cBid) and truncated Bid (tBid), it disrupts MOM integrity via Bax/Bak-dependent and independent mechanisms. Apoptosis plays a dual role in viral infections, either promoting or counteracting viral propagation. Consequently, viruses modulate Bid signaling to favor their replication. The deregulation of Bid activity contributes to oncogenic transformation, inflammation, immunosuppression, neurotoxicity, and pathogen propagation during various viral infections. In this work, we explore Bid’s structure, function, activation processes, and mitochondrial targeting. We describe its role in apoptosis induction and its involvement in infections with multiple viruses. Additionally, we discuss the therapeutic potential of Bid in antiviral strategies. Understanding Bid’s signaling pathways offers valuable insights into host–virus interactions and the pathogenesis of infections. This knowledge may facilitate the development of novel therapeutic approaches to combat virus-associated diseases effectively.

Green coffee extract is currently of great interest to researchers due to its high concentration of chlorogenic acid (CGA) and its potential health benefits. CGA constitutes 6 to 10% of the dry weight of the extract and, due to its anti-inflammatory properties, is a promising natural supplement and agent with therapeutic applications. The purpose of our study was to discover the effects of CGA on peripheral blood mononuclear cell proliferation, and the production of pro- and anti-inflammatory cytokines as well as reactive oxidative species (ROS) in horses during exercise. According to the findings, CGA can affect the proliferation of T helper cells. In addition, at a dose of 50 g/mL, CGA increased the activation of CD4+FoxP3+ and CD8+FoxP3+ regulatory cells. Physical activity decreases ROS production in CD5+ monocytes, but this effect depends on the concentration of CGA, and the effect of exercise on oxidative stress was lower in CD14+ than in CD5+ cells. Regardless of CGA content, CGA significantly increased the release of the anti-inflammatory cytokine IL-10. Moreover, the production of IL-17 was greater in cells treated with 50 g/mL of CGA from beginners compared to the control and advanced groups of horses. Our findings suggest that CGA may have immune-enhancing properties. This opens new avenues of research into the mechanisms of action of CGA and possible applications in prevention and health promotion in sport animals.

Dendritic cells (DCs) are among the first immune cells to detect viral invasion and play a central role in initiating and shaping antiviral immune responses. Many innate and adaptive immune functions of DCs are regulated by cathepsins, proteolytic enzymes primarily found in acidic endolysosomal compartments. Different DC subsets exhibit distinct cathepsin expression patterns, influencing their functional capacities and interactions with viruses. In DCs, cathepsins contribute to virus sensing through innate receptors, regulate cytokine production and DC migration, and are essential for viral antigen degradation and loading onto MHC molecules for T-cell activation. Many viruses, however, have evolved mechanisms to alter cathepsin expression and activity, thereby subverting DC function and promoting their own persistence. Indeed, cathepsins can facilitate viral entry into DCs, promote viral replication, and support immune evasion strategies. In this review, we summarize recent advances in understanding the role of cathepsins in DC–virus interactions, emphasizing both how DCs exploit cathepsins to generate protective immune responses and how viruses manipulate cathepsin activity to their advantage. We particularly focus on clinically relevant viral pathogens, including HIV, influenza virus, hepatitis C virus, human cytomegalovirus, Ebola virus, and SARS-CoV-2, to illustrate the multifaceted influence of cathepsins on DC biology during viral infection.

Neutrophils are first-line immune effectors in innate immunity, employing migration, phagocytosis, and neutrophil extracellular trap (NET) formation to combat infections and mediate inflammatory responses. NET formation, the regulated extrusion of chromatin and antimicrobial proteins, is crucial for pathogen clearance but can lead to pathological inflammation when dysregulated. Cathepsins, a diverse family of proteolytic enzymes traditionally associated with lysosomal protein degradation, have emerged as key modulators of neutrophil functions. Serine cathepsins, including cathepsin G, and cysteine cathepsins, such as cathepsin C, regulate neutrophil migration, chemokine processing, and serine protease maturation, thereby orchestrating effective phagocytosis and antimicrobial activity. These enzymes also influence NET formation, linking classical lysosomal proteolysis to specialized immune responses. This review synthesizes current evidence on cathepsin-mediated regulation of neutrophil effector functions, highlighting their dual role in host defense and disease pathology, and discusses their potential as therapeutic targets for mitigating NET-driven inflammation in conditions such as autoimmune diseases, cancer metastasis, and ischemia–reperfusion injury.

Apoptosis is a natural mechanism that shapes morphogenesis and helps maintain tissue homeostasis in healthy organisms. It is also extensively studied in the context of pathologies such as cancer and viral infections. The course of the latter strictly depends on host cell viability; therefore, regulators of apoptosis may play essential roles in distinct viral infections as well as virus-dependent diseases. The p53-upregulated modulator of apoptosis (PUMA), a pro-apoptotic member of the B-cell lymphoma 2 (Bcl-2) family, directly disrupts mitochondrial integrity, thereby promoting the intrinsic apoptotic pathway. PUMA-mediated cell death act as a double-edged sword that may either facilitate viral infection and its consequences or counteract them, depending on the infectious agent and the complex context of pathogen–host interactions. Accordingly, various viruses have evolved strategies to modulate host cell viability to their advantage by targeting PUMA—either by suppressing transcription of the PUMA gene, binding and inactivating the PUMA protein, or, conversely, inducing its production. In this work, we describe the role of PUMA in infections caused by distinct viruses and in associated diseases, viral strategies for modulating PUMA-related signaling pathways, and potential therapeutic implications.