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Computational and machine learning frameworks have greatly contributed to early diagnosis and rapid therapeutic interventions due to breakthroughs in science and technology. This study aims to develop a mathematical model that utilizes machine learning and integrates both innate and adaptive immunological components to examine the progression of breast cancer. The proposed framework utilizes a set of ordinary differential equations to represent the interactions between breast cancer cells, cytotoxic T lymphocytes, T-helper cells, and macrophages. We used machine learning optimization techniques to enhance the computational framework, enabling accurate modeling of the dynamic alterations occurring in the tumor microenvironment. This approach also considers the different properties and responses of immune cells. Our validated results, obtained using metaheuristic algorithms and sensitivity analysis, provide significant insights into the correlation between the advancement of breast cancer and the innate and adaptive immune systems. This study supports the theory that advanced programming tools may enhance healthcare systems by offering reliable techniques for understanding and possibly controlling the progression of cancer via the manipulation of the immune system. [ABSTRACT FROM AUTHOR]

An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that the Ru(II) complex can initiate the oncosis‐associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis promotes dendritic cell maturation and awakens adaptive cytotoxic T lymphocytes but also activates the innate immune by inducing the polarization of macrophages towards an M1 phenotype. [ABSTRACT FROM AUTHOR]

An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that the Ru(II) complex can initiate the oncosis‐associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis promotes dendritic cell maturation and awakens adaptive cytotoxic T lymphocytes but also activates the innate immune by inducing the polarization of macrophages towards an M1 phenotype. [ABSTRACT FROM AUTHOR]

Chemical pollution poses a significant threat to human health, with detrimental effects on various physiological systems, including the respiratory, cardiovascular, mental, and perinatal domains. While the impact of pollution on these systems has been extensively studied, the intricate relationship between chemical pollution and immunity remains a critical area of investigation. The focus of this study is to elucidate the relationship between chemical pollution and human immunity. To accomplish this task, this study presents a comprehensive review that encompasses in vitro, ex vivo, and in vivo studies, shedding light on the ways in which chemical pollution can modulate human immunity. Our aim is to unveil the complex mechanisms by which environmental contaminants compromise the delicate balance of the body's defense systems going beyond the well-established associations with defense systems and delving into the less-explored link between chemical exposure and various immune disorders, adding urgency to our understanding of the underlying mechanisms and their implications for public health. [ABSTRACT FROM AUTHOR]

The ubiquitous soil-associated fungus Cryptococcus neoformans causes pneumonia that may progress to fatal meningitis. Recognition of fungal cell walls by C-type lectin receptors (CLRs) has been shown to trigger the host immune response. Caspase recruitment domain-containing protein 9 (Card9) is an intracellular adaptor that is downstream of several CLRs. Experimental studies have implicated Card9 in host resistance against C. neoformans; however, the mechanisms that are associated with susceptibility to progressive infection are not well defined. To further characterize the role of Card9 in cryptococcal infection, Card9em1Sq mutant mice that lack exon 2 of the Card9 gene on the Balb/c genetic background were created using CRISPR-Cas9 genome editing technology and intratracheally infected with C. neoformans 52D. Card9em1Sq mice had significantly higher lung and brain fungal burdens and shorter survival after C. neoformans 52D infection. Susceptibility of Card9em1Sq mice was associated with lower pulmonary cytokine and chemokine production, as well as reduced numbers of CD4+ lymphocytes, neutrophils, monocytes, and dendritic cells in the lungs. Histological analysis and intracellular cytokine staining of CD4+ T cells demonstrated a Th2 pattern of immunity in Card9em1Sq mice. These findings demonstrate that Card9 broadly regulates the host inflammatory and immune response to experimental pulmonary infection with a moderately virulent strain of C. neoformans. [ABSTRACT FROM AUTHOR]

According to the data from the World Health Organization, about 800 million of the world population had contracted coronavirus infection caused by SARS-CoV-2 by mid-2023. Properties of this virus have allowed it to circulate in the human population for a long time, evolving defense mechanisms against the host immune system. Severity of the disease depends largely on the degree of activation of the systemic immune response, including overstimulation of macrophages and monocytes, cytokine production, and triggering of adaptive T- and B-cell responses, while SARS-CoV-2 evades the immune system actions. In this review, we discuss immune responses triggered in response to the SARS-CoV-2 virus entry into the cell and malfunctions of the immune system that lead to the development of severe disease. [ABSTRACT FROM AUTHOR]

This article discusses the roles of innate and adaptive immunity in providing protection against COVID-19 through inactivated viral vaccines. The emergence of the Omicron variant has raised concerns about immune evasion and the effectiveness of existing vaccination strategies. Studies have shown that administering a third dose of an mRNA or inactivated vaccine can reduce the severity of symptoms and mortality. The research highlights the importance of adaptive immunity, particularly CD4+ T-cell memory pools, in responding to SARS-CoV-2 infections. Additionally, the article explores the role of innate immunity, including monocytes, dendritic cells, and natural killer cells, in the initial defense against viral infections. The study also suggests that inactivated vaccines can induce "trained immunity" in myeloid cells, enhancing their functionality and antiviral response. Overall, this research provides valuable insights into the immunomodulatory effects of inactivated virus vaccines and can inform future vaccine development and immunization strategies. [Extracted from the article]

Obesity is one of the most pressing healthcare concerns of the twenty-first century. Obesity prevalence has risen dramatically in recent decades, and in 2016, more than 1.9 billion adults were overweight (BMI ≥ 25 kg/m2) and 650 million were obese (BMI ≥ 30 kg/m2). About 50% of the world's population is anticipated to be obese/overweight within the next decade. Obesity is a major risk factor for a variety of non-communicable diseases, including type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, and a variety of malignancies. Obesity has emerged as a substantial risk factor for hospitalization and death from viral respiratory infections such as influenza A and the ongoing pandemic SARS-CoV-2. Several independent studies have indicated that obese/overweight patients are at a higher risk of severe disease and death from these respiratory diseases. Excess fat, particularly visceral fat, contributes to the development of a variety of metabolic disorders, including persistent systemic inflammation and decreased immunological function. As a result, the immunological response to infectious pathogens is weakened, resulting in poorer outcomes post-infection. Additionally, the poor lung mechanics associated with obesity may increase the risk of more serious respiratory infections. In this review, we address the likely mechanism(s) that predispose obese people to severe diseases caused by viral respiratory infections. [ABSTRACT FROM AUTHOR]

Simple Summary: Sea Turtles have a unique immune system, which evolved over millions of years in the persistent host-pathogen arms race. As this species occupies a unique evolutionary and environmental niche, they provide an opportunity to gain insight into the evolution of immunity. We present an overview of the turtle immune system, including the cells and organs important for coordinating the immune response to pathogens, with a focus on pathogen recognition and inflammatory mediators, including Interferons. We highlight areas for future study and note which studies have investigated freshwater turtles and are lacking in sea turtles. We particularly focus on the Green Sea turtle (Chelonia mydas) as the juvenile turtles within this species are the most afflicted by the neoplastic tumorous disease, fibropapillomatosis (FP). The immune system of sea turtles is not completely understood. Sea turtles (as reptiles) bridge a unique evolutionary gap, being ectothermic vertebrates like fish and amphibians and amniotes like birds and mammals. Turtles are ectotherms; thus, their immune system is influenced by environmental conditions like temperature and season. We aim to review the turtle immune system and note what studies have investigated sea turtles and the effect of the environment on the immune response. Turtles rely heavily on the nonspecific innate response rather than the specific adaptive response. Turtles' innate immune effectors include antimicrobial peptides, complement, and nonspecific leukocytes. The antiviral defense is understudied in terms of the diversity of pathogen receptors and interferon function. Turtles also mount adaptive responses to pathogens. Lymphoid structures responsible for lymphocyte activation and maturation are either missing in reptiles or function is affected by season. Turtles are a marker of health for their marine environment, and their immune system is commonly dysregulated because of disease or contaminants. Fibropapillomatosis (FP) is a tumorous disease that afflicts sea turtles and is thought to be caused by a virus and an environmental factor. We aim, by exploring the current understanding of the immune system in turtles, to aid the investigation of environmental factors that contribute to the pathogenesis of this disease and provide options for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Antibody affinity maturation in vertebrates requires the enzyme activation-induced cytidine deaminase (AID) which initiates secondary antibody diversification by mutating the immunoglobulin loci. AID-driven antibody diversification is conserved across jawed vertebrates since bony and cartilaginous fish. Two exceptions have recently been reported, the Pipefish and Anglerfish, in which the AID-encoding aicda gene has been lost. Both cases are associated with unusual reproductive behavior, including male pregnancy and sexual parasitism. Several cold water fish in the Atlantic cod (Gadinae) family carry an aicda gene that encodes for a full-length enzyme but lack affinity-matured antibodies and rely on antibodies of broad antigenic specificity. Hence, we examined the functionality of their AID. Results: By combining genomics, transcriptomics, immune responsiveness, and functional enzymology of AID from 36 extant species, we demonstrate that AID of that Atlantic cod and related fish have extremely lethargic or no catalytic activity. Through ancestral reconstruction and functional enzymology of 71 AID enzymes, we show that this enzymatic inactivation likely took place relatively recently at the emergence of the true cod family (Gadidae) from their ancestral Gadiformes order. We show that this AID inactivation is not only concordant with the previously shown loss of key adaptive immune genes and expansion of innate and cell-based immune genes in the Gadiformes but is further reflected in the genomes of these fish in the form of loss of AID-favored sequence motifs in their immunoglobulin variable region genes. Conclusions: Recent demonstrations of the loss of the aicda gene in two fish species challenge the paradigm that AID-driven secondary antibody diversification is absolutely conserved in jawed vertebrates. These species have unusual reproductive behaviors forming an evolutionary pressure for a certain loss of immunity to avoid tissue rejection. We report here an instance of catalytic inactivation and functional loss of AID rather than gene loss in a conventionally reproducing vertebrate. Our data suggest that an expanded innate immunity, in addition to lower pathogenic pressures in a cold environment relieved the pressure to maintain robust secondary antibody diversification. We suggest that in this unique scenario, the AID-mediated collateral genome-wide damage would form an evolutionary pressure to lose AID function. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a–C5aR1–glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a–C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. These results reveal a common involvement of the complement and glycosphingolipid systems driving immune inflammation and tissue damage in COVID-19 and GD, respectively. It is therefore expected that combined targeting of the complement and sphingolipid pathways could ameliorate the tissue destruction, organ failure, and death in patients at high-risk of developing severe cases of COVID-19. [ABSTRACT FROM AUTHOR]

Identified in the late nineteenth century as a single species residing on human skin, Malassezia is now recognized as a diverse genus comprising 18 species inhabiting not only skin but human gut, hospital environments, and even deep-sea sponges. All cultivated Malassezia species are lipid dependent, having lost genes for lipid synthesis and carbohydrate metabolism. The surging interest in Malassezia results from development of tools to improve sampling, culture, identification, and genetic engineering, which has led to findings implicating it in numerous skin diseases, Crohn disease, and pancreatic cancer. However, it has become clear that Malassezia plays a multifaceted role in human health, with mutualistic activity in atopic dermatitis and a preventive effect against other skin infections due to its potential to compete with skin pathogens such as Candida auris. Improved understanding of complex microbe-microbe and host-microbe interactions will be required to define Malassezia's role in human and animal health and disease so as to design targeted interventions. [ABSTRACT FROM AUTHOR]

Identified in the late nineteenth century as a single species residing on human skin, Malassezia is now recognized as a diverse genus comprising 18 species inhabiting not only skin but human gut, hospital environments, and even deep-sea sponges. All cultivated Malassezia species are lipid dependent, having lost genes for lipid synthesis and carbohydrate metabolism. The surging interest in Malassezia results from development of tools to improve sampling, culture, identification, and genetic engineering, which has led to findings implicating it in numerous skin diseases, Crohn disease, and pancreatic cancer. However, it has become clear that Malassezia plays a multifaceted role in human health, with mutualistic activity in atopic dermatitis and a preventive effect against other skin infections due to its potential to compete with skin pathogens such as Candida auris. Improved understanding of complex microbe-microbe and host-microbe interactions will be required to define Malassezia's role in human and animal health and disease so as to design targeted interventions. [ABSTRACT FROM AUTHOR]

Purpose: Particular interest is now given to the potential of dietary supplements as alternative non-pharmacological approaches in intestinal inflammation handling. In this aim, this study evaluates the efficiency of fish collagen peptides, Naticol®Gut, on colonic inflammation. Methods: Wild type and Mannose receptor-deficient in the myeloid lineage C57BL/6 mice were administered with Dextran Sodium Sulfate (DSS), Naticol®Gut, DSS, and Naticol®Gut or only water for 4 or 8 days. Inflammatory status was evaluated by establishing macroscopic and microscopic scores, by measuring cytokine and calprotectin production by ELISA and the myeloperoxidase activity by chemiluminescence. Colonic macrophages were phenotyped by measuring mRNA levels of specific markers of inflammation and oxidative status. Colonic immune populations and T-cell activation profiles were determined by flow cytometry. Mucosa-associated gut microbiota assessment was undertaken by qPCR. The phenotype of human blood monocytes from inflammatory bowel disease (IBD) subjects was characterized by RT-qPCR and flow cytometry and their oxidative activity by chemiluminescence. Results: Naticol®Gut-treated DSS mice showed attenuated colonic inflammation compared to mice that were only exposed to DSS. Naticol®Gut activity was displayed through its ability to orient the polarization of colonic macrophage towards an anti-inflammatory and anti-oxidant phenotype after its recognition by the mannose receptor. Subsequently, Naticol®Gut delivery modulated CD4 T cells in favor of a Th2 response and dampened CD8 T-cell activation. This immunomodulation resulted in an intestinal eubiosis. In human monocytes from IBD subjects, the treatment with Naticol®Gut also restored an anti-inflammatory and anti-oxidant phenotype. Conclusion: Naticol®Gut acts as a protective agent against colitis appearing as a new functional food and an innovative and complementary approach in gut health. [ABSTRACT FROM AUTHOR]

Burn injuries are among the most common peacetime injuries, with mortality ranging from 2.3% to 3.6%. At the same time, 85–90% of patients with burns are people of working age and children. Burn injury leads to metabolic disorders and systemic inflammatory response, inefficient energy consumption, and other physiological changes that can lead to dysfunction of organs and systems. The most formidable complication of burn injuries is sepsis mediated by multiple organ failure, the most common cause of poor prognosis in patients and has specific differences in these injuries. The purpose of this article was to dwell in detail on the most promising immunobiochemical markers of sepsis in the format of a mini-review, based on the main aspects of the immunopathogenesis of this complication. The pathogenesis of a burn injury and any general pathological process is based on an inflammatory reaction and large-scale changes in the skin and mucous membranes. This review is devoted to the progress in understanding the main aspects of the immunopathogenesis of burn lesions and the features of post-burn immune dysfunction, manifested by disorders in the innate and adaptive immunity systems. Attention is focused on the role in the immunopathogenesis of the development of systemic and local disorders in burn injury. Characterization of primary immunobiochemical markers of burn injury (cytokines, growth factors, C-reactive protein, procalcitonin, presepsin, matrix metalloproteinases, reactive oxygen species, nitric oxide, hemostasis parameters) is presented. The problem of treating burn lesions is associated with constant monitoring of the condition of patients and regular monitoring of specific immunobiochemical markers predicting sepsis for the timely initiation of a specific therapy. [ABSTRACT FROM AUTHOR]

Invasive Candida albicans (CA) infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings from our lab indicate that taurocholic acid (TCA), a major bile acid present in the intestine, promotes CA colonization and dissemination. Here, we report that oral administration of TCA to CA-infected mice significantly decreased the number of mononuclear phagocytes and CD4+ IL17A+ T helper 17 cells that play a critical role in controlling CA in the intestine. Collectively, our results indicate that TCA modulates mucosal innate and adaptive immune responses to promote CA colonization in the intestine. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID‐19) pandemic started in March 2020 and caused over 5 million confirmed deaths worldwide as far August 2021. We have been recently overwhelmed by a wide literature on how the immune system recognizes severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and contributes to COVID‐19 pathogenesis. Although originally considered a respiratory viral disease, COVID‐19 is now recognized as a far more complex, multi‐organ‐, immuno‐mediated‐, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response at the start, or in advanced disease, a high innate‐induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus‐driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently applied to some inflammatory disorders as asthma, rhinosinusitis with polyposis, and atopic dermatitis, herein we suggest defining different endo‐types and the related phenotypes along COVID‐19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo‐type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a pathologic immune-mediated remodelling of the vasculature in transplanted hearts and, by impairing perfusion, is the major cause of late graft loss. Although best understood following cardiac transplantation, similar forms of allograft vasculopathy occur in other vascularized organ grafts and some features of CAV may be shared with other immune-mediated vasculopathies. Here, we describe the incidence and diagnosis, the nature of the vascular remodelling, immune and non-immune contributions to pathogenesis, current therapies, and future areas of research in CAV. [ABSTRACT FROM AUTHOR]

Kefiran is a water-soluble polysaccharide well recognized as a bioactive ingredient to enhance nutritional and health-promoting features. Also, some therapeutic properties have made this macromolecule an active ingredient in ointments and oral anti-inflammatory drugs. However, the details of the molecular and cellular aspects of these effects have not been addressed. In this study, lipopolysaccharides (LPS)-induced monocytes, lymphocytes, and monocyte-derived dendritic cells (MDDCs) as representative cells for both innate and adaptive immunity were treated with kefiran for 2 h. Kefiran had an anti-inflammatory effect on monocytes to reduce pro-inflammatory cytokines, interleukin 1 β (IL-1β) & tumor necrosis factor α (TNF-α), as well as nuclear factor kappa b (NF-kb). However, it did not affect lymphocytes. Overexpression of Toll-like receptor 4 (TLR4) in LPS-induced cells was not reduced after kefiran treatment. Kefiran balanced MDDCs secretion of pro/anti-inflammatory cytokines by reducing and enhancing the expression of IL-1β and interleukin 10 (IL-10), respectively. Also, kefiran decreased the number of apoptotic immature MDDCs and promoted dose-dependent phagocytosis capacity of MDDCs. According to the results of the current study, it may be concluded that the immunomodulatory effects of kefiran are due to antagonist against innate immune receptors especially TLR4. The results of this study can be used as a guide to developing kefiran-based non-aggressive anti-inflammatory drugs. Furthermore, understanding the immunobiological effects of kefiran on monocytes and lymphocytes was another outcome of this study. Unlabelled Image [ABSTRACT FROM AUTHOR]

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double‐strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule‐targeted therapies and, in recent years, immunotherapy (IT). Cancer‐cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T‐cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic mechanisms. Therefore, many efforts are being made in order to reach a better understanding of the innate immunity reactions after radiation therapy (RT) and the design of new combinatorial IT strategies focused in these particular populations. [ABSTRACT FROM AUTHOR]

The social, health, and economic challenges of a steadily increasing aging population demand the use of appropriate translational animal models to address questions like healthy aging, vaccination strategies, or potential interventions during the aging process. Due to their genetic proximity to humans, especially nonhuman primates (NHPs) with a relatively short generation period compared to humans, qualify as excellent animal models for these purposes. The use of common marmosets (Callithrix jacchus) in gerontology research steadily increased over the last decades, yet important information about their aging parameters are still missing. We therefore aimed to characterize their aging immune system by comprehensive flow cytometric phenotyping of blood immune cells from juvenile, adult, aging, and geriatric animals. Aged and geriatric animals displayed clear signs of immunosenescence. A decline in CD4/CD8 ratio, increased expression of HLA‐DR and PD‐1, higher frequencies of CD95+ memory cells, alterations in cytokine secretion, and a decline in the proliferative capacity proved T cell senescence in aging marmosets. Also, the B cell compartment was affected by age‐related changes: while overall B cell numbers remained stable with advancing age, expression of the activation marker CD80 increased and immunoglobulin M expression decreased. Interestingly, marmoset B cell memory subset distribution rather mirrored the human situation than that of other NHP. CD21+ CD27− naïve B cell frequencies decreased while those of CD21− CD27− tissue memory B cells increased with age. Furthermore, frequencies and numbers of NK cells as part of the innate immune system declined with advancing age. Thus, the observed immunological changes in common marmosets over their life span revealed several similarities to age‐related changes in humans and encourages further studies to strengthen the common marmoset as a potential aging model. Research Highlights: Immunological investigations of the aging process in common marmosets revealed changes in different immune cell subsets.Due to similar immunological changes during aging, this species is proposed as a potential translational animal model in gerontology research. [ABSTRACT FROM AUTHOR]

This review seeks to provide an update of preclinical findings and available clinical data on the chronic persistent inflammation and its direct role on the pulmonary arterial hypertension (PAH) progression. We reviewed the different mechanisms by which the inflammatory and immune pathways contribute to the structural and functional changes occurring in the three vascular compartments: the tunica intima, tunica media, and tunica adventitia. We also discussed how these inflammatory mediator changes may serve as a biomarker of the PAH progression and summarize unanswered questions and opportunities for future studies in this area. [ABSTRACT FROM AUTHOR]

Vaccinal prophylaxis is the most effective way to reduce incidence rates. However, the immune response developing after injection of most inactivated vaccines is insufficient when used without adjuvants. Special attention should be paid to the issue of immunoprophylaxis of high-risk patients with impaired immune status. Use of appropriate adjuvants during vaccination can optimize development of protective immunity in immunocompromised patients. Cytokines that regulate in vivo immune-response cascades to any antigenic stimulus and influence the development of an antigen-specific immune response can be considered as potential immunoadjuvants. The present review analyzes briefly studies of the immunoadjuvant properties of cytokines used to increase the effectiveness of regularly scheduled vaccines and those used for epidemic indications. [ABSTRACT FROM AUTHOR]

Anthracenedione is a derivative of anthraquinone aromatic organic natural pigments found in senna, aloe latex, rhubarb, cascara, lichens, and fungi having broad range of bioactivity, including anti-cancer, anti-inflammatory, anti-microbial, anti-fungal, anti-oxidant, anti-viral activities suggesting potential for clinical purpose of many diseases. The effect of anthracenedione enriched diet on growth, hematology, innate and adaptive immune parameters as well as protection from Aeromonas hydrophila in Mystus vittatus was reported. The weight gain, feed intake, specific growth rate (SGR), and feed conversion ratio (FCR) were significantly increased in uninfected groups fed with 5 mg kg−1 diet. The red blood cells (RBC) and white blood cells (WBC) count and the percentage of lymphocytes were significantly augmented in both infected and uninfected groups feeding with any diet. The percentage of monocytes, eosinophils, neutrophils and the biochemical profile such as total protein, albumin, and globulin also were significantly increased in the infected and uninfected groups fed with 5 mg kg−1 enriched diet. The innate and adaptive immune parameters such as phagocytic activity, immunoglobulin M (IgM), respiratory burst activity, complement activity, and lysozyme activity were significantly increased in uninfected and infected groups fed with 5 or 10 mg kg−1 diets but not with 1 mg kg−1 diet. The serum superoxide dismutase (SOD) activity is significantly increased in the uninfected and infected fish fed with 5 mg kg−1 diet but the increase was not significantly observed in 1 or 10 mg kg−1 diets. The nitric oxide (NO) production is significantly elevated in both uninfected and infected groups fed with 5 mg kg−1 diet. On the other hand, the lymphocyte proliferation and myeloperoxidase (MPO) activity were significantly increased the infected and uninfected groups fed with 5 and 10 mg kg−1 diets. The cumulative mortality was found 5% with 1 and 5 mg kg−1 diet groups while it was observed 10% mortality with 10 mg kg−1 diet group. Based on the results, it is observed that feeding the uninfected and infected groups with 5 mg kg−1 anthracenedione diet resulted in better improvement of growth, hematological, biochemical, and innate as well as adaptive immune parameters in M. vittatus against A. hydrophila. • Improved weight gain, feed intake, SGR, FCR with 2 mg kg−1 diet. • Hemato-biochemical improved infected and noninfected fish fed with 2 mg kg−1. • All immunological parameter were significantly with 2 and 5 mg kg−1 diets. • Mortality was 5% with 1 and 2 mg kg−1 diet while it was 10% mortality with 2 mg kg−1 diet. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is the most common skin cancer with an incidence that has been rapidly increasing in the past decades. Melanomas are among the most immunogenic tumors and, as such, have the greatest potential to respond favorably to immunotherapy. However, like many cancers, melanomas acquire various suppressive mechanisms, which generally act in concert, to escape innate and adaptive immune detection and destruction. Intense research into the cellular and molecular events associated with melanomagenesis, which ultimately lead to immune suppression, has resulted in the discovery of new therapeutic targets and synergistic combinations of immunotherapy, targeted therapy and chemotherapy. Tremendous effort to determine efficacy of single and combination therapies in pre-clinical and clinical phase I-III trials has led to FDA-approval of several immunotherapeutic agents that could potentially be beneficial for aggressive, highly refractory, advanced and metastatic melanomas. The increasing availability of approved combination therapies for melanoma and more rapid assessment of patient tumors has increased the feasibility of personalized treatment to overcome patient and tumor heterogeneity and to achieve greater clinical benefit. Here, we review the evolution of the immune system during melanomagenesis, mechanisms exploited by melanoma to suppress anti-tumor immunity and methods that have been developed to restore immunity. We emphasize that an effective therapeutic strategy will require coordinate activation of tumor-specific immunity as well as increased recognition and accessibility of melanoma cells in primary tumors and distal metastases. This review integrates available knowledge on melanoma-specific immunity, molecular signaling pathways and molecular targeting strategies that could be utilized to envision therapeutics with broader application and greater efficacy for early stage and advanced metastatic melanoma. [ABSTRACT FROM AUTHOR]

Macrophages play an important role in tissue development and homeostasis. They serve as a nexus between adaptive and innate immunity, and employ considerable plasticity. In cancer, they play a pivotal role in chronic inflammation and tumor growth either by directly stimulating the proliferation of cancer cells or by producing angiogenic and lymphangiogenic factors. Although numerous immune cells play an important role in the tumor microenvironment, tumor-associated macrophages (TAMs) are by far the most extensively studied. A better understanding of the role of TAMs in mediating chemo- and radiotherapy resistance and suppressing immunosurveillance has led to numerous strategies targeting TAMs as an anticancer therapy either by targeting them directly or by polarizing TAMs toward a tumoricidal phenotype. [ABSTRACT FROM AUTHOR]

Lymphocytes and heterophils are the two most abundant leucocyte types, which play a major role in adaptive and innate immune defence, respectively. The ratio of heterophils to lymphocytes (H/L ratio) may reflect a readiness to cope with infection through injury (via heterophils) rather than with a communicable disease (via lymphocytes). Since elevated H/L ratio constitutes a corticosterone‐mediated response to external stressors, this trait is generally acknowledged as the robust measure of physiological stress in vertebrates.Here, I hypothesized that baseline H/L ratios of birds (as measured under normal physiological function) could be an important evolutionary trait shaped by species' ecology and life history. I predicted that H/L ratios should be determined by traits related to pathogen exposure (migratoriness, sociality, breeding latitude) and trade‐offs between investment in reproduction (clutch size) and self‐maintenance (longevity).I compiled published data on leucocyte profiles for nearly 250 bird species representing over half of all extant avian orders and nearly 30% of all extant avian families. Phylogenetically informed comparative methods were used to assess evolutionary associations of H/L ratios with ecological and life‐history traits across the avian tree of life.Relatively strong phylogenetic signal and phylogenetic autocorrelation in avian H/L ratios indicated that most diversification in this trait occurred relatively early in bird radiation. Fluctuating selection and drift were identified as the major forces responsible for the evolution of H/L ratios in birds, while low H/L ratios were identified as an ancestral state in birds. Finally, phylogenetically informed Bayesian models showed that H/L ratios correlated negatively with longevity and positively with sociality and breeding latitude.This study was the first to describe the patterns of avian H/L ratio evolution in a broad phylogenetic framework. The results indicate that H/L ratios should not be merely recognized as a proxy for the intraspecific variation in physiological stress, but also as an important evolutionary trait, which probably have adaptive significance visible in a wider phylogenetic perspective. The study is the first to describe the patterns of avian heterophil/lymphocyte (H/L) ratio evolution in a broad phylogenetic framework. The results indicate that H/L ratios should not be merely recognized as a proxy for the physiological stress, but also as an important evolutionary trait of possible adaptive significance. [ABSTRACT FROM AUTHOR]

Vaccines remain one of the most important pillars in preventative medicine, providing protection against a wide array of diseases by inducing humoral and/or cellular immunity. Of the many possible candidate antigens for subunit vaccine development, carbohydrates are particularly appealing because of their ubiquitous presence on the surface of all living cells, viruses, and parasites as well as their known interactions with both innate and adaptive immune cells. Indeed, several licensed vaccines leverage bacterial cell-surface carbohydrates as antigens for inducing antigen-specific plasma cells secreting protective antibodies and the development of memory T and B cells. Carbohydrates have also garnered attention in other aspects of vaccine development, for example, as adjuvants that enhance the immune response by either activating innate immune responses or targeting specific immune cells. Additionally, carbohydrates can function as immunomodulators that dampen undesired humoral immune responses to entire protein antigens or specific, conserved regions on antigenic proteins. In this review, we highlight how the interplay between carbohydrates and the adaptive and innate arms of the immune response is guiding the development of glycans as vaccine components that act as antigens, adjuvants, and immunomodulators. We also discuss how advances in the field of synthetic glycobiology are enabling the design, engineering, and production of this new generation of carbohydrate-containing vaccine formulations with the potential to prevent infectious diseases, malignancies, and complex immune disorders. • Glycans play a role in nearly every aspect of innate and adaptive immunology. • Many licensed vaccines leverage bacterial cell-surface carbohydrates as antigens. • Many glycans are used as adjuvants that enhance immune responses. • Glycans are used as delivery systems that promote specific immune cell or tissues. • Glycans are used as dampeners that suppress undesired humoral immune responses. [ABSTRACT FROM AUTHOR]

One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer-membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4/myeloid differentiation factor-2 complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, mass spectrometry-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications. [ABSTRACT FROM AUTHOR]

The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site. We also discuss the effect of APOBEC oligomerization on functionality. Future structural studies will need to address how ssDNA binding away from the active site may enhance catalysis and the mechanism by which RNA binding may modulate catalytic activity on ssDNA. [ABSTRACT FROM AUTHOR]

Abstract: To maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota‐dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut‐derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno‐ or microbe‐targeted therapies. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a highly contagious bacterial infection caused by Mycobacterium tuberculosis (Mtb) , which has been ranked as the second leading cause of death worldwide from a single infectious agent. As an intracellular pathogen , Mtb has well adapted to the phagocytic host microenvironment, influencing diverse host processes such as gene expression, trafficking, metabolism, and signaling pathways of the host to its advantage. These responses are the result of dynamic interactions of the bacteria with the host cell signaling pathways, whereby the bacteria attenuate the host cellular processes for their survival. Specific host genes and the mechanisms involved in the entry and subsequent stabilization of M. tuberculosis intracellularly have been identified in various genetic and chemical screens recently. The present understanding of the co-evolution of Mtb and macrophage system presented us the new possibilities for exploring host-directed therapeutics (HDT). Here, we discuss the host-pathogen interaction for Mtb , including the pathways adapted by Mtb to escape immunity. The review sheds light on different host-directed therapies (HDTs) such as repurposed drugs and vitamins, along with their targets such as granuloma, autophagy, extracellular matrix, lipids, and cytokines, among others. The article also examines the available clinical data on these drug molecules. In conclusion, the review presents a perspective on the current knowledge in the field of HDTs and the need for additional research to overcome the challenges associated HDTs. [ABSTRACT FROM AUTHOR]

Background and aim Lipoprotein-apheresis (LA) is a therapeutic approach used against severe forms of dyslipidemia in patients who are non-responders or intolerant to pharmacological treatments. However, little is known about the potential pleiotropic effects of LA, particularly regarding the immune system and its regulation. Thus, in an attempt to analyse the potential effects of dyslipidemia and LA on the regulation of CD4 + T cells activation and lineage differentiation, we compared the CD4 + T cells cytokines secretion profiles of dyslipidemic patients before and after LA with the profiles observed in healthy donors. Methods CD4 + T cells were isolated from 5 LA patients and 5 healthy donors and activated with anti-CD3 or anti-CD3 + anti-CD46 antibodies. The supernatants were collected after 36 h incubation and levels of secreted cytokines analysed by flow cytometry. Results Our results revealed a deep remodelling of CD4 + T cells cytokines secretion patterns in dyslipidemic patients compared to healthy donors, as reflected by a 15 times higher IFN-γ secretion rate after CD3 + CD46 co-activation in dyslipidemic patients after LA compared to healthy subjects and 8 times higher after CD3 activation alone ( p = 0.0187 and p = 0.0118 respectively). Moreover, we demonstrated that LA itself also modifies the phenotype and activation pattern of CD4 + T-cells in dyslipidemic patients. Conclusion These observations could be of fundamental importance in the improvement of LA columns/systems engineering and in developing new therapeutic approaches regarding dyslipidemia and associated pathologies such as atherosclerosis and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs), also called Tumor Initiating Cells (TICs), can be defined as cancer cells that are present within solid tumors or hematological cancers, which have characteristics associated with normal stem cells, but which can give rise to all cell types found in a particular cancer sample. CSCs, therefore, are transformed stem cells, which can self-renew, differentiate into diverse progenies, and drive continuous tumor growth (Kreso & Dick, , Cell Stem Cell, 14:275-291; Schatton et al., , Nature, 451:345-349; Villani, Sabbatino, Ferrone, & Ferrone, , Melanoma Management, 2:109-114; Zhou et al., , Drug Discovery, 8:806-823) (Fig. ). [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is a contagious epizootic pathogen adversely affecting porcine industry in Asian and European countries. Till date, 8 serotypes and 24 genotypes of the virus have been reported. Few live attenuated virus vaccine studies have reported to provide complete protection against ASFV infection but biohazard concern still remain. Recombinant subunit antigens are capable of providing cellular and humoral immunity in porcine, but not a single vaccine has hit the market yet. In the present study, we attempted to use recombinant Salmonella Typhimurium JOL912 strain harboring ASFV antigens (rSal-ASFV) to investigate its immunostimulant effect in porcine. Post intramuscular administration, we observed significant increment in the levels of helper T cells, cytotoxic T cells, natural killer (NK) cells, and immunoglobulin (i.e. IgG, IgA, and IgM) levels in rSal-ASFV treated groups. Further RT-PCR analysis indicated the increased expression of MHC-I, MHC-II, CD80/86, NK cell receptors (NKp30, NKp44, and NKp46) and cytokines while ELIspot analysis revealed significant production of IFN-γ in rSal-ASFV treated groups. Taken together, we are able to demonstrate that rSal-ASFV could elicit a non-specific cellular as well as humoral immune response. However, additional antigen specific immunity data is needed to evaluate its efficacy. Intramuscular administration of rSal-ASFV was found to be safe and immunostimulant in nature without any side-effects and may serve as an excellent option for in-vivo antigen delivery in pigs. [Display omitted] • Recombinant Salmonella was used for administration of ASFV antigens. • Salmonella inoculation was safe, devoid of any side-effects with zero mortality. • Administration of recombinant Salmonella induced a non-specific immune response. • ELIspot assay revealed significant interferon (IFN-γ) secretion in treated groups. [ABSTRACT FROM AUTHOR]

Background: Much of the morbidity associated with short bowel syndrome (SBS) is attributed to effects of decreased enteral nutrition and administration of total parenteral nutrition (TPN). We hypothesized that acute SBS alone has significant effects on gene expression beyond epithelial proliferation, and tested this in a zebrafish SBS model. Methods: In a model of SBS in zebrafish (laparotomy, proximal stoma, distal ligation, n = 29) or sham (laparotomy alone, n = 28) surgery, RNA-Seq was performed after 2 weeks. The proximal intestine was harvested and RNA isolated. The three samples from each group with the highest amount of RNA were spiked with external RNA controls consortium (ERCC) controls, sequenced and aligned to reference genome with gene ontology (GO) enrichment analysis performed. Gene expression of ctnnb1, ccnb1, ccnd1, cyp7a1a, dkk3, ifng1-2, igf2a, il1b, lef1, nos2b, saa1, stat3, tnfa and wnt5a were confirmed to be elevated in SBS by RT-qPCR. Results: RNA-seq analysis identified 1346 significantly upregulated genes and 678 significantly downregulated genes in SBS zebrafish intestine compared to sham with Ingenuity analysis. The upregulated genes were involved in cell proliferation, acute phase response signaling, innate and adaptive immunity, bile acid regulation, production of nitric oxide and reactive oxygen species, cellular barrier and coagulation. The downregulated genes were involved in folate synthesis, gluconeogenesis, glycogenolysis, fatty-acid oxidation and activation and drug and steroid metabolism. RT-qPCR confirmed gene expression differences from RNA-Sequencing. Conclusion: Changes of gene expression after 2 weeks of SBS indicate complex and extensive alterations of multiple pathways, some previously implicated as effects of TPN. The systemic sequelae of SBS alone are significant and indicate multiple targets for investigating future therapies. [ABSTRACT FROM AUTHOR]

Since its discovery 75 years ago, a wealth of knowledge has accumulated on the role of cardiolipin, the hallmark phospholipid of mitochondria, in bioenergetics and particularly on the structural organization of the inner mitochondrial membrane. A surge of interest in this anionic doubly-charged tetra-acylated lipid found in both prokaryotes and mitochondria has emerged based on its newly discovered signaling functions. Cardiolipin displays organ, tissue, cellular and transmembrane distribution asymmetries. A collapse of the membrane asymmetry represents a pro-mitophageal mechanism whereby externalized cardiolipin acts as an “eat-me” signal. Oxidation of cardiolipin's polyunsaturated acyl chains - catalyzed by cardiolipin complexes with cytochrome c . - is a pro-apoptotic signal. The messaging functions of myriads of cardiolipin species and their oxidation products are now being recognized as important intracellular and extracellular signals for innate and adaptive immune systems. This newly developing field of research exploring cardiolipin signaling is the main subject of this review. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. [ABSTRACT FROM AUTHOR]

Elevated concentrations of Nt-pro-BNP were revealed in 11% of apparently healthy subjects aged 19-24 years and 22% of middle-aged (34-55 years) subjects. An increase in Nt-pro-BNP blood concentration was detected in 90% of patients with metabolic syndrome. Elevated levels of Nt-pro-BNP in peripheral blood occur with age. Higher concentrations of the peptide were revealed in women. Inhibition of lymphocytes proliferation and differentiation accompanied by increasing concentration of Nt-pro-BNP in blood is associated with a deficiency of the IL-2 level due to increased IL-10 concentration. Immunosuppressive effect of IL-10 declares itself at the level of innate immune reactions as a decrease in blood counts of naive CD45RA+ T lymphocytes, natural killer cells, T cells with adhesion receptor ( CD56+) and adhesion receptor ligand ( CD62L+). To prevent a loss of the intercellular pool, the effect of Nt-pro-BNP is activated. No statistically significant correlations between the increased Nt-pro-BNP concentration in blood and the content of serum IgM, IgG, IgA, IgE, IL-6, TNF-α, IFN-γ, CEC C1q, or С3d, as well as glucose, hemoglobin, transferrin, iron, or free fatty acids were revealed in apparently healthy subjects. [ABSTRACT FROM AUTHOR]

There is an emerging interest to develop human vaccines against medically-important fungal pathogens and a need for a preclinical animal model to assess vaccine efficacies and protective correlates. HLA-DR4 (DRB1∗0401 allele) transgenic mice express a human major histocompatibility complex class II (MHC II) receptor in such a way that CD4 + T-cell response is solely restricted by this human molecule. In this study HLA-DR4 transgenic mice were immunized with a live-attenuated vaccine (ΔT) and challenged by the intranasal route with 50–70 Coccidioides posadasii spores, a potentially lethal dose. The same vaccination regimen offers 100% survival for C57BL/6 mice. Conversely, ΔT-vaccinated HLA-DR4 mice displayed 3 distinct manifestations of Coccidioides infection including 40% fatal acute (FAD), 30% disseminated (DD) and 30% pulmonary disease (PD). The latter 2 groups of mice had reduced loss of body weight and survived to at least 50 days postchallenge (dpc). These results suggest that ΔT vaccinated HLA-DR4 mice activated heterogeneous immunity against pulmonary Coccidioides infection. Vaccinated HLA-DR4 mice displayed early expansion of Th1 and Th17 cells and recruitment of inflammatory innate cells into Coccidioides -infected lungs during the first 9 dpc. While contraction rates of Th cells and the inflammatory response during 14–35 dpc significantly differed among the 3 groups of vaccinated HLA-DR4 mice. The FAD group displayed a sharply reduced Th1 and Th17 response, while overwhelmingly recruiting neutrophils into lungs during 9–14 days. The FAD group approached moribund by 14 dpc. In contrast, vaccinated HLA-DR4 survivors gradually contracted Th cells and inflammatory response with the greatest rate in the PD group. While vaccinated HLA-DR4 mice are susceptible to Coccidioides infection, they are useful for evaluation of vaccine efficacy and identification of immunological correlates against this mycosis. [ABSTRACT FROM AUTHOR]

The spectrum of Clostridium difficile infections is highly variable, ranging from asymptomatic carriage to fatal colitis depending on the strain virulence and on the host, its gut microbiota and its immune response. After disruption of the gut microbiota, C. difficile pathogenesis can be divided into three steps: 1) contamination by spores and their germination; 2) multiplication of vegetative cells and intestinal colonization using colonization factors; 3) production of the toxins TcdA and TcdB, and for some strains, the binary toxin, which are responsible for the clinical signs. Three lines of defense counteract C. difficile . The first line is the epithelial barrier, which is breached by the toxins. Then, a rapid innate immune response follows, which forms the second line of defense. It provides very quick defense reactions against C. difficile but is non-specific and does not confer memory. C. difficile and its virulence factors, the toxins and colonization factors, induce a highly pro-inflammatory response, which can be either beneficial or harmful, but triggers the adaptive immunity as the third line of defense required to control the infectious process. Adaptive immunity provides a highly specific immune response against C. difficile with memory and long lasting immunity. The innate and adaptive immune responses against the toxins and surface components are analyzed as well as their role in disease susceptibility, severity and recurrences. [ABSTRACT FROM AUTHOR]

Effective drug selection is the current challenge in rheumatoid arthritis (RA). Treatment failure may follow different pathomechanisms and therefore require investigation of molecularly defined subgroups. In this exploratory study, whole blood transcriptomes of 68 treatment-naïve early RA patients were analyzed before initiating MTX. Subgroups were defined by serologic and genetic markers. Response related signatures were interpreted using reference transcriptomes of various cell types, cytokine stimulated conditions and bone marrow precursors. HLA-DRB4-negative patients exhibited most distinctive transcriptional differences. Preponderance of transcripts associated with phagocytes and bone marrow activation indicated response and transcripts of T- and B-lymphocytes non-response. HLA-DRB4-positive patients were more heterogeneous, but also linked failure to increased adaptive immune response. RT-qPCR confirmed reliable candidate selection and independent samples of responders and non-responders the functional patterning. In summary, genomic stratification identified different molecular pathomechanisms in early RA and preponderance of innate but not adaptive immune activation suggested response to MTX therapy. [ABSTRACT FROM AUTHOR]

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years. [ABSTRACT FROM AUTHOR]

The aim of the work was to evaluate long-term results of studies focusing on improving methods for preventing and treating fish diseases using selected natural and syntetic immunomodulators and vaccines in fish culture. Simultaneously, attention is drawn to infectious or environmental threats against which appropriately composed immunoprophylaxis can be used in production cycles. Fish culture is intensifying in Poland and globally, which means that the role of prevention and well-designed prophylaxis is of increasing significance to the prevention and treatment of fish diseases. Currently, 33 fish species are cultured in Poland as stocking material or for production. The primary methods for preventing diseases in controlled fish culture are ensuring the welfare of fish and other prophylactic methods, including immunoprophylaxis. Many infectious and non-infectious threats that can cause direct losses and limit fish culture are present in the aquatic environment. Fish diseases generally stem from the simultaneous action of many factors that coincide and are difficult to distinguish. Pesticides (organochlorine insecticides, organophosphorus herbicides), aromatic hydrocarbons, pentachlorophenol, heavy metals, and chemotherapeutics are particularly toxic to fish. Biodegradation, which is continual in aquatic environments, is a process by which toxic and other substances that negatively affect fish become bioavailable and impact the immune system, the functioning of which is a specific bioindicator of environmental quality. Innate immunity plays a key role in the defense against disadvantageous factors, which also include pathogens. Immunomodulation methods can protect resistance mechanisms, thereby increasing disease prevention and treatment in controlled fish culture. [ABSTRACT FROM AUTHOR]

The tight control of the innate and adaptive immune responses in the stomach mucosa during chronic Helicobacter pylori infection is of prime importance for the bacteria to persist and for the host to prevent inflammation-driven diseases. This review summarizes recent data on the roles of innate and adaptive immune responses during H. pylori/host interactions. In addition, the latest preclinical developments of H. pylori vaccines are discussed with a special focus on the clinical trial reported by Zeng et al., who provided evidence that oral vaccination significantly reduces the acquisition of natural H. pylori infection in children. [ABSTRACT FROM AUTHOR]

Background Common marmosets are extensively used in immunological and pharmacological research, and the usage of methods such as flow cytometry gain increasing importance. Methods Using multicolor flow cytometry cross-reactivity of monoclonal antibodies with cells of common marmosets was analyzed. Furthermore, frequencies of immune cells and immunological parameters were assessed in healthy common marmosets. Results A total of 97 clones of monoclonal antibodies raised against CD markers, chemokine receptors, and miscellaneous markers were tested. Additionally, baseline frequencies of different innate and adaptive immune cells as well as certain parameters, such as activation and memory T-cell and B-cell distribution, are provided. Conclusion Our study gives an extended overview of cross-reactive antibodies for flow cytometric analysis of immune cells as well as baseline values for different immune parameters in healthy common marmosets. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) comprise an emerging cancer therapeutic modality whose activity involves both direct tumor cell lysis and the induction of immunogenic cell death (ICD). Cellular proteins released from the OV-lysed tumor cells, known as damage-associated molecular patterns and tumor-associated antigens, activate dendritic cells and elicit adaptive antitumor immunity. Interaction with the innate immune system and the development of long-lasting immune memory also contribute to OV-induced cell death. The degree to which the ICD component contributes to the clinical efficacy of OV therapy is still unclear. Modulation of a range of immune interactions may be beneficial or detrimental in nature and the interactions depend on the specific tumor, the site and extent of the disease, the immunosuppressive tumor microenvironment, the OV platform, the dose, time, and delivery conditions, as well as individual patient responses. To enhance the contribution of ICD, OVs have been engineered to express immunostimulatory genes and strategies have been developed to combine OV therapy with chemo- and immune-based therapeutic regimens. However, these approaches carry the risk that they may also be tolerogenic depending on their levels and the presence of other cytokines, their direct antiviral effects, and the timing and conditions of their expression. The contribution of autophagy to adaptive immunity, the ability of the OVs to kill cancer stem cells, and the patient's baseline immune status are additional considerations. This review focuses on the complex and as yet poorly understood balancing act that dictates the outcome of OV therapy. We summarize current understanding of the OVs' function in eliciting antitumor immunity and its relationship to therapeutic efficacy. Also discussed are the criteria involved in restraining antiviral immune responses and minimizing pathology while promoting antitumor immunity to override immune tolerance. [ABSTRACT FROM AUTHOR]

Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies. [ABSTRACT FROM AUTHOR]

Background: Arcobacter (A.) butzleri has been described as causative agent for sporadic cases of human gastroenteritis with abdominal pain and acute or prolonged watery diarrhea. In vitro studies revealed distinct adhesive, invasive and cytotoxic properties of A. butzleri. Information about the underlying immunopathological mechanisms of infection in vivo, however, are scarce. The aim of this study was to investigate the immunopathological properties of two different A. butzleri strains in a well-established murine infection model. Results: Gnotobiotic IL-10-/- mice, in which the intestinal microbiota was depleted by broad-spectrum antibiotic treatment, were perorally infected with two different A. butzleri strains isolated from a diseased patient (CCUG 30485) or fresh chicken meat (C1), respectively. Eventhough bacteria of either strain could stably colonize the intestinal tract at day 6 and day 16 postinfection (p.i.), mice did not exert infection induced symptoms such as diarrhea or wasting. In small intestines of infected mice, however, increased numbers of apoptotic cells could be detected at day 16, but not day 6 following infection with either strain. A strain-dependent influx of distinct immune cell populations such as T and B cells as well as of regulatory T cells could be observed upon A. butzleri infection which was accompanied by increased small intestinal concentrations of pro-inflammatory cytokines such as TNF, IFN-γ, MCP-1 and IL-6. Remarkably, inflammatory responses following A. butzleri infection were not restricted to the intestinal tract, given that the CCUG 30485 strain induced systemic immune responses as indicated by increased IFN-γ concentrations in spleens at day 6, but not day 16 following infection. Conclusion: Upon peroral infection A. butzleri stably colonized the intestinal tract of gnotobiotic IL-10-/- mice. The dynamics of distinct local and systemic inflammatory responses could be observed in a strain-dependent fashion pointing towards an immunopathogenic potential of A. butzleri in vivo. These results indicate that gnotobiotic IL-10-/- mice are well suited to further investigate the molecular mechanisms underlying arcobacteriosis in vivo. [ABSTRACT FROM AUTHOR]

It has been known for decades that the immune system has a tremendous impact on behavior. Most work has described the negative role of immune cells on the central nervous system. However, we and others have demonstrated over the last decade that a well-regulated immune system is needed for proper brain function. Here we discuss several neuro-immune interactions, using examples from brain homeostasis and disease states. We will highlight our understanding of the consequences of malfunctioning immunity on neurodevelopment and will discuss the roles of the innate and adaptive immune system in neurodevelopment and how T cells maintain a proper innate immune balance in the brain surroundings and within its parenchyma. Also, we describe how immune imbalance impairs higher order brain functioning, possibly leading to behavioral and cognitive impairment. Lastly, we propose our hypothesis that some behavioral deficits in neurodevelopmental disorders, such as in autism spectrum disorder, are the consequence of malfunctioning immunity. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease . [ABSTRACT FROM AUTHOR]