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OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. RESULTS: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). CONCLUSION: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.

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Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (β-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.

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Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

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Objectives: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. Methods: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. Results: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). Conclusion: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged. Systematic review registration: PROSPERO CRD42021279246.

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Cancer immunotherapies include monoclonal antibodies, cytokines, oncolytic viruses, cellular therapies, and other biological and synthetic immunomodulators. These are traditionally studied for their effect on the immune system's role in eliminating cancer cells. However, some of these therapies have the unique ability to directly induce cytotoxicity in cancer cells by inducing immunogenic cell death (ICD). Unlike general immune stimulation, ICD triggers specific therapy-induced cell death pathways, based on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells. These activate innate pattern recognition receptors (PRRs) and subsequent adaptive immune responses, offering the promise of sustained anticancer drug efficacy and durable antitumour immune memory. Exploring how onco-immunotherapies can trigger ICD, enhances our understanding of their mechanisms and potential for combination strategies. This review explores the complexities of these immunotherapeutic approaches that induce ICD, highlighting their implications for the innate immune system, addressing challenges in cancer treatment, and emphasising the pivotal role of ICD in contemporary cancer research.

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Classically, particle-induced periprosthetic osteolysis at the implant-bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+) coexisting with CD68+/TRAP- multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.

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The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

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Recently, it has been described that innate immune cells such as monocytes, macrophages, and natural killer cells can develop a non-specific immune response induced by different stimuli, including lipopolysaccharides, Mycobacterium bovis Bacillus Calmette-Guérin, and oxidized low-density lipoprotein. This non-specific immune response has been named "trained immunity," whose mechanism is essential for host defense and vaccine response, promoting better infection control. However, limited information about trained immunity in other non-infectious diseases, such as autoimmune illness, has been reported. The complexity of autoimmune pathology arises from dysfunctions in the innate and adaptive immune systems, triggering different clinical outcomes depending on the disease. Nevertheless, T and B cell function dysregulation is the most common characteristic associated with autoimmunity by promoting the escape from central and peripheral tolerance. Despite the importance of adaptative immunity to autoimmune diseases, the innate immune system also plays a prominent and understudied role in these pathologies. Accordingly, epigenetic and metabolic changes associated with innate immune cells that undergo a trained process are possible new therapeutic targets for autoimmune diseases. Even so, trained immunity can be beneficial or harmful in autoimmune diseases depending on several factors associated with the stimuli. Here, we reviewed the role of trained immunity over the innate immune system and the possible role of these changes in common autoimmune diseases, including Systemic Lupus Erythematosus, Rheumatoid Arthritis, Multiple Sclerosis, and Type 1 Diabetes.

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The emergence of multidrug-resistant bacterial strains with respect to commercially available antimicrobial drugs has marked a watershed in treatment therapies to fight pathogens and has stimulated research on alternative remedies. Proteins of the innate immune system of mammals have been highlighted as potentially yielding possible treatment options for infections. Lactoferrin (Lf) is one of these proteins; interestingly, no resistance to it has been found. Lf is a conserved cationic nonheme glycoprotein that is abundant in milk and is also present in low quantities in mucosal secretions. Moreover, Lf is produced and secreted by the secondary granules of neutrophils at infection sites. Lf is a molecule of approximately 80 kDa that displays multiple functions, such as antimicrobial, anti-viral, anti-inflammatory, and anticancer actions. Lf can synergize with antibiotics, increasing its potency against bacteria. Lactoferricins (Lfcins) are peptides resulting from the N-terminal end of Lf by proteolytic cleavage with pepsin. They exhibit several anti-bacterial effects similar to those of the parental glycoprotein. Synthetic analog peptides exhibiting potent antimicrobial properties have been designed. The aim of this review is to update understanding of the structure and effects of Lf and Lfcins as anti-bacterial compounds, focusing on the mechanisms of action in bacteria and the use of Lf in treatment of infections in patients, including those studies where no significant differences were found. Lf could be an excellent option for prevention and treatment of bacterial diseases, mainly in combined therapies with antibiotics or other antimicrobials.

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Venoms are products of specialized glands and serve many living organisms to immobilize and kill prey, start digestive processes and act as a defense mechanism. Venoms affect different cells, cellular structures and tissues, such as skin, nervous, hematological, digestive, excretory and immune systems, as well as the heart, among other structures. Components of both the innate and adaptive immune systems can be stimulated or suppressed. Studying the effects on the cells and molecules produced by the immune system has been useful in many biomedical fields. The effects of venoms can be the basis for research and development of therapeutic protocols useful in the modulation of the immunological system, including different autoimmune diseases. This review focuses on the understanding of biological effects of diverse venom on the human immune system and how some of their components can be useful for the study and development of immunomodulatory drugs.

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