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Introduction: An effective vaccination policy must be implemented to prevent foot-and-mouth disease (FMD). However, the currently used vaccines for FMD have several limitations, including induction of humoral rather than cellular immune responses. Methods: To overcome these shortcomings, we assessed the efficacy of levamisole, a small-molecule immunomodulator, as an adjuvant for the FMD vaccine. We conducted in vitro studies using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs) and in vivo studies using mice (experimental animals) and pigs (target animals). We evaluated levamisole-mediated modulation of the innate and adaptive immune responses; early, mid-term, and long-term immune-inducing effects; modes of action; and host defense against viral infection. Results: Levamisole treatment promoted IFNγ secretion in murine PECs and porcine PBMCs. Additionally, it induced robust and long-lasting immune responses by eliciting high antibody titers and high virus-neutralizing antibody titers. By activating downstream signaling pathways of various pattern-recognition receptors, levamisole stimulated the expression of multiple cytokines and costimulatory molecules. Owing to these immunostimulatory effects, levamisole elicited host defense against viral infections in pigs. Our findings demonstrate the potential of levamisole as an immunostimulatory agent. Discussion: The results also indicate that levamisole, as an adjuvant for animal vaccines, can elicit robust innate and adaptive immune responses, thereby enhancing host defense against viral infections. This study provides a promising approach for the development of improved FMD vaccine strategies in the future. [ABSTRACT FROM AUTHOR]

Introduction: Many countries use commercial foot-and-mouth disease (FMD) vaccines to prevent FMD pandemics, but these vaccines have disadvantages, such as repeated vaccinations due to the short persistence of antibody (Ab) titers and incomplete host defense despite high Ab titers. To address these shortcomings, we aimed to develop a novel FMD vaccine containing furfurman as an adjuvant. Method: To demonstrate the efficacy of the test vaccine, adaptive immunity was evaluated by measuring Ab and neutralizing Ab titers and host defense against viral infections in experimental and target animals. In addition, the expression levels of cytokines [interferon (IFN)α, IFNβ, IFNγ, interleukin (IL)-1β, IL-2, and IL-12p40] were evaluated at the early stages of vaccination to confirm the simultaneous induction of cellular and humoral immune responses induced by the test vaccine. Result: The groups that received vaccine containing furfurman showed a strong early, mid-term, and long-term immune response and host defense against viral infections compared to the control groups. The significant upregulation observed in cytokine levels in the furfurman group compared to those in the control groups strongly suggest that the test vaccine strengthens cellular immune response and effectively induces a humoral immune response. Conclusion: Our study demonstrated that furfurman, as an FMD vaccine adjuvant, achieves long-lasting immunity and host defense against viral infections by eliciting potent cellular and humoral immune responses. Therefore, our findings contribute to the design of next-generation FMD vaccines and highlight the potential application of furfurman as an adjuvant for other viral diseases. [ABSTRACT FROM AUTHOR]

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]

IntroductionAn effective vaccination policy must be implemented to prevent foot-and-mouth disease (FMD). However, the currently used vaccines for FMD have several limitations, including induction of humoral rather than cellular immune responses.MethodsTo overcome these shortcomings, we assessed the efficacy of levamisole, a small-molecule immunomodulator, as an adjuvant for the FMD vaccine. We conducted in vitro studies using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs) and in vivo studies using mice (experimental animals) and pigs (target animals). We evaluated levamisole-mediated modulation of the innate and adaptive immune responses; early, mid-term, and long-term immune-inducing effects; modes of action; and host defense against viral infection.ResultsLevamisole treatment promoted IFNγ secretion in murine PECs and porcine PBMCs. Additionally, it induced robust and long-lasting immune responses by eliciting high antibody titers and high virus-neutralizing antibody titers. By activating downstream signaling pathways of various pattern-recognition receptors, levamisole stimulated the expression of multiple cytokines and costimulatory molecules. Owing to these immunostimulatory effects, levamisole elicited host defense against viral infections in pigs. Our findings demonstrate the potential of levamisole as an immunostimulatory agent.DiscussionThe results also indicate that levamisole, as an adjuvant for animal vaccines, can elicit robust innate and adaptive immune responses, thereby enhancing host defense against viral infections. This study provides a promising approach for the development of improved FMD vaccine strategies in the future.

IntroductionMany countries use commercial foot-and-mouth disease (FMD) vaccines to prevent FMD pandemics, but these vaccines have disadvantages, such as repeated vaccinations due to the short persistence of antibody (Ab) titers and incomplete host defense despite high Ab titers. To address these shortcomings, we aimed to develop a novel FMD vaccine containing furfurman as an adjuvant.MethodTo demonstrate the efficacy of the test vaccine, adaptive immunity was evaluated by measuring Ab and neutralizing Ab titers and host defense against viral infections in experimental and target animals. In addition, the expression levels of cytokines [interferon (IFN)α, IFNβ, IFNγ, interleukin (IL)-1β, IL-2, and IL-12p40] were evaluated at the early stages of vaccination to confirm the simultaneous induction of cellular and humoral immune responses induced by the test vaccine.ResultThe groups that received vaccine containing furfurman showed a strong early, mid-term, and long-term immune response and host defense against viral infections compared to the control groups. The significant upregulation observed in cytokine levels in the furfurman group compared to those in the control groups strongly suggest that the test vaccine strengthens cellular immune response and effectively induces a humoral immune response.ConclusionOur study demonstrated that furfurman, as an FMD vaccine adjuvant, achieves long-lasting immunity and host defense against viral infections by eliciting potent cellular and humoral immune responses. Therefore, our findings contribute to the design of next-generation FMD vaccines and highlight the potential application of furfurman as an adjuvant for other viral diseases.

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]

Obesity‐induced chronic low‐grade inflammation, also known as metaflammation, results from alterations of the immune response in metabolic organs and contributes to the development of fatty liver diseases and type 2 diabetes. The diversity of tissue‐resident leukocytes involved in these metabolic dysfunctions warrants an in‐depth immunophenotyping in order to elucidate disease etiology. Here, we present a 30‐color, full spectrum flow cytometry panel, designed to (i) identify the major innate and adaptive immune cell subsets in murine liver and white adipose tissues and (ii) discriminate various tissue‐specific myeloid subsets known to contribute to the development of metabolic dysfunctions. This panel notably allows for distinguishing embryonically‐derived liver‐resident Kupffer cells from newly recruited monocyte‐derived macrophages and KCs. Furthermore, several adipose tissue macrophage (ATM) subsets, including perivascular macrophages, lipid‐associated macrophages, and pro‐inflammatory CD11c+ ATMs, can also be identified. Finally, the panel includes cell‐surface markers that have been associated with metabolic activation of different macrophage and dendritic cell subsets. Altogether, our spectral flow cytometry panel allows for an extensive immunophenotyping of murine metabolic tissues, with a particular focus on metabolically‐relevant myeloid cell subsets, and can easily be adjusted to include various new markers if needed. [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]

Extracellular vesicles (EVs) are nanosized particles released by nearly every cell type across all kingdoms of life. As a result, EVs are ubiquitously present in various human body fluids. Composed of a lipid bilayer, EVs encapsulate proteins, nucleic acids, and metabolites, thus playing a crucial role in immunity, for example, by enabling intercellular communication. More recently, there has been increasing evidence that EVs can also act as key regulators of allergic immune responses. Their ability to facilitate cell‐to‐cell contact and to transport a variety of different biomolecules enables active modulation of both innate and adaptive immune processes associated with allergic reactions. A comprehensive understanding of the intricate mechanisms underlying the interactions among allergens, immune cells, and EVs is imperative to develop innovative strategies for controlling allergic responses. This review highlights the recent roles of host cell‐ and bacteria‐derived EVs in allergic diseases, presenting experimental and clinical evidence that underscores their significance. Additionally, the therapeutic potential of EVs in allergy management is outlined, along with the challenges associated with targeted delivery and cargo stability for clinical use. Optimization of EV composition and targeting strategies holds promise for advancing translational applications and establishing EVs as biomarkers or safe therapeutics for assessing allergic reactions. For these reasons, EVs represent a promising avenue for advancing both our understanding and management of allergic immune processes. [ABSTRACT FROM AUTHOR]

Background: Commercial foot-and-mouth disease (FMD) vaccines have limitations, such as local side effects, periodic vaccinations, and weak host defenses. To overcome these limitations, we developed a novel FMD vaccine by combining an inactivated FMD viral antigen with the small molecule isoprinosine, which served as an adjuvant (immunomodulator). Method: We evaluated the innate and adaptive immune responses elicited by the novel FMD vaccine involved both in vitro and in vivo using mice and pigs. Results: We demonstrated isoprinosine-mediated early, mid-term, and long-term immunity through in vitro and in vivo studies and complete host defense against FMD virus (FMDV) infection through challenge experiments in mice and pigs. We also elucidated that isoprinosine induces innate and adaptive (cellular and humoral) immunity via promoting the expression of immunoregulatory gene such as pattern recognition receptors [PRRs; retinoic acid-inducible gene (RIG)-I and toll like receptor (TLR)9], transcription factors [T-box transcription factor (TBX)21, eomesodermin (EOMES), and nuclear factor kappa B (NF-kB)], cytokines [interleukin (IL)-12p40, IL- 23p19, IL-23R, and IL-17A)], and immune cell core receptors [cluster of differentiation (CD)80, CD86, CD28, CD19, CD21, and CD81] in pigs. Conclusion: These findings present an attractive strategy for constructing novel FMD vaccines and other difficult-to-control livestock virus vaccine formulations based on isoprinosine induced immunomodulatory functions. [ABSTRACT FROM AUTHOR]

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2±0.7% vs. 23.1±2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0±1.3% vs. 36.0±3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1±0.8% vs. 82.3±0.4%) or rRBD (94.6±0.3% vs. 82.3±0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Current SLE therapies include immunosuppressants, antimalarial drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, but these treatments can cause substantial toxicities to organs and may not be effective for all patients. In recent years, significant progress has been made in the treatment of SLE using immunotherapy, including Benlysta and Saphnelo. These advances in immunotherapy hold promise for SLE patients, providing new therapeutic options that may offer better clinical benefit and effectiveness. Simultaneously, several new biological therapies focusing on cytokines, peptides, targeted antibodies, and cell-based approaches are under clinical evaluation and have shown immense potential for the treatment of SLE. However, the complexity of SLE immunopathogenesis and disease heterogeneity present significant challenges in the development of effective immunological therapies. This review aims to discuss past experiences and understanding of diverse immunological targeting therapies for SLE and highlight future perspectives for the development of novel immunological therapies.

Objective: to assess the dynamics of the immune system functioning when using mesotherapy with peptide complexes. Materials and methods: the observation group consisted of 26 women (from 35 to 55 years old) who received a course of mesotherapy with preparations containing peptides for the first time. Injections were carried out in a course of 5 procedures with an interval of 14 days. The exclusion criteria were the absence of same manipulations in the past, hormone replacement therapy, combined oral contraceptives, pregnancy, lactation, acute infections, somatic pathologies. The parameters of innate and adaptive immunity were studied before the course of procedures, right after it, 3 and 6 months after the course. Skin quality changes were assessed using the Aramo Smart Lite 300 dermatoscope. Results: improved skin quality, decreased skin creases, increased skin moisture. The obtained clinical improvements last for three months after the end of the course and there is a tendency for the effects to decrease after six months. In the functioning of the immune system, there is a redistribution of lymphocytes population in the peripheral bloodstream immediately after the course of mesotherapy. In addition, an increase in peripheral T-regulatory lymphocytes responsible for intraimmune suppression was documented. The activation of spontaneous oxygen-producing activity was noted. 3 months after the procedure, no significant changes in immunological parameters were found. 6 months after the course of procedures, a decrease in the level of T-lymphocytes with an increase in the expression of markers of early T-cell activation was recorded. In the humoral link, an increase in circulating B-lymphocytes was documented. In the parameters of innate immunity, there is a decrease in the spontaneous oxygen-producing activity of neutrophils. Conclusion: as a result of the study, a positive persistent clinical effect is documented, simultaneously with the mobilization of factors of innate and adaptive immunity. It is important to note the fact that the immune response restores completely within 6 months after a course of mesotherapy with peptide complexes, with still noticeable clinical results.

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]

High‐dimensional immunoprofiling is essential for studying host response to immunotherapy, infection, and disease in murine model systems. However, the difficulty of multiparameter panel design combined with a lack of existing murine tools has prevented the comprehensive study of all major leukocyte phenotypes in a single assay. Herein, we present a 40‐color flow cytometry panel for deep immunophenotyping of murine lymphoid tissues, including the spleen, blood, Peyer's patches, inguinal lymph nodes, bone marrow, and thymus. This panel uses a robust set of surface markers capable of differentiating leukocyte subsets without the use of intracellular staining, thus allowing for the use of cells in downstream functional experiments or multiomic analyses. Our panel classifies T cells, B cells, natural killer cells, innate lymphoid cells, monocytes, macrophages, dendritic cells, basophils, neutrophils, eosinophils, progenitors, and their functional subsets by using a series of co‐stimulatory, checkpoint, activation, migration, and maturation markers. This tool has a multitude of systems immunology applications ranging from serial monitoring of circulating blood signatures to complex endpoint analysis, especially in pre‐clinical settings where treatments can modulate leukocyte abundance and/or function. Ultimately, this 40‐color panel resolves a diverse array of immune cells on the axes of time, tissue, and treatment, filling the niche for a modern tool dedicated to murine immunophenotyping. [ABSTRACT FROM AUTHOR]

Objectives. No sulfated polysaccharides (fucoidans) has been declared as the pharmaceutical substances, adjuvants, etc., which is associated with the problems of obtaining the structurally characterized and homogeneous samples or their oligomeric fractions that retain high biological activity. The highly purified fucoidan with regular reproducible structural characteristics (F1) was obtained by enzymatic hydrolysis of native fucoidan (F2). Aim. The comparative study of fucoidans from the brown alga Fucus evanescens (F1 and F2) effects on the effector functions of innate and adaptive immunity cells loaded with ovalbumin (OVA) in vitro and in vivo. Material and methods. Fucoidan F1 — the enzymatically modified product of native fucoidan; F2 — the native fucoidan. The fucoidans effects on the expression level of the main immunophenotypic markers of innate and adaptive immunity (neutrophils, monocytes, natural killers, lymphocytes) cells in vitro were studied by methods of flow cytometry. The fucoidans effects on the production of serum OVA-specific antibodies (IgG, IgG1, IgG2а) and cytokines (IFNγ, IL-2, IL-10, IL-12) were detected in BALB/c mice immunized with OVA. Results. The tested fucoidans activate the effector functions of innate and adaptive immunity cells loaded with OVA in vitro and act as adjuvants, stimulating both Th1 (IgG2а, INFγ, IL-2) and Th2 (IgG1, IL-10) immune response to OVA in vivo. Conclusions. The immunoadjuvant effect of the enzymatically modified fucoidan (F1) on effector functions of innate and adaptive immunity cells are comparable to those of the native fucoidan (F2). The findings determine the possibility of F1 use as an adjuvant for a wide range of prophylactic and therapeutic vaccines.

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2 ± 0.7% vs. 23.1 ± 2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0 ± 1.3% vs. 36.0 ± 3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1 ± 0.8% vs. 82.3 ± 0.4%) or rRBD (94.6 ± 0.3% vs. 82.3 ± 0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness. [ABSTRACT FROM AUTHOR]

In this article we present the role and discuss the significance of monocytes in both innate and adaptive immunity. Monocytes are the largest white blood cells of convoluted, bilobed nuclei. Growth factors and cytokines determine the monocyte subtype. The monocyte functional and phenotype heterogeneity have been recognized and in the recent years there have been identified their major populations in humans; classical (CD14+CD16−), non-classical (CD14dim CD16+), and intermediate (CD14+CD16+). Each of these subpopulations is distinguished by the expression of distinct surface markers and by their functions in homeostasis and disease. Monocytes develop in bone marrow and travel to tissues and organs in where they become macrophages or dendritic cells. Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. Dendritic cells represent a heterogeneous family of immune cells that link innate and adaptive immunity. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. Monocytes differentiated into dendritic cells play an important role in innate and adaptive immunity, due to their microbicidal potential, capacity to stimulate CD4+ and CD8+ T-cell responses and ability to regulate immunoglobulins production by B cells. [ABSTRACT FROM AUTHOR]

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 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.

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2 ± 0.7% vs. 23.1 ± 2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0 ± 1.3% vs. 36.0 ± 3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1 ± 0.8% vs. 82.3 ± 0.4%) or rRBD (94.6 ± 0.3% vs. 82.3 ± 0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness. [ABSTRACT FROM AUTHOR]

Background: Most commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety. Objectives: To address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection. Methods: We demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan. Results: β-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host's innate and adaptive immunity. Conclusion: Our study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine's safety and efficacy, it represents a breakthrough among next-generation FMD vaccines. [ABSTRACT FROM AUTHOR]

Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of •NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a rare subtype of non‐Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In‐depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD‐1/PD‐L1&PD‐L2, TIGIT/PVR, CD137/CD137‐L, CTLA‐4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies. [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]

Sepsis is a life-threatening condition caused by dysregulated host immune response to infection, leading to persistent inflammation followed by immunosuppression. Sepsis represents a substantial global health problem owing to protracted inflammation, immune suppression, and susceptibility to nosocomial infections. Despite continuing progress in the development of antibiotics, fluid resuscitation, and other supportive care therapies, no specific immunomodulatory drugs or immunotherapeutic adjuncts for the treatment of sepsis are available to date. The advances in tertiary care facilities and patient care have improved the survival of sepsis patients in the initial hyper-inflammatory phase of sepsis. However, the majority of sepsis patients succumb later due to prolong immunosuppression. The sepsis-induced immune dysregulation and its long-term effects on mortality are under meticulous investigations that are still poorly defined. Sepsis leads to the impaired functions of the innate and adaptive immune systems. The exhaustion of T cells, reduced expression of human leukocytes antigen (HLA)-DR on monocytes, and induced uncontrolled apoptosis of immune cells have been reported as hallmark features of sepsis. Sepsis-induced immune cell apoptosis of immune cells is a primary contributing factor to the immunosuppression in sepsis. Preclinical studies have identified several new therapeutic targets for therapy in sepsis, including monoclonal antibodies (Abs) and anti-apoptotic agents to reduce T cells exhaustion, immune cells apoptosis, and restoring immune cells functions. Recent studies have centered on immune-modulatory therapy. The review article will focus solely on sepsis’ effects on innate and adaptive cells functions that contribute to immunosuppression. Finally, it is discussed how immune cells responsible for immunosuppression might be directly targeted to provide potential therapeutic benefits in treating sepsis and improving long-term survival.

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]

The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans. [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]

In relation to ancient infections, a substantial number of retroviral sequences with persistent immunogenic potential were integrated within the human genome (HERVs). Under physiological conditions, coding sequences from HERVs can participate in cell/tissue homeostasis and physiological functions in an epigenetically controlled manner. However, HERV expression is susceptible to contribute to various pathologies, including autoinflammatory and autoimmune disorders, when reprogrammed by exogenous stimuli such as drugs or microbial infections. Both innate and adaptive components of the immune system can be mobilized in response to deregulated/de-repressed expression of HERV determinants and thereby, modify immune tolerance to tissue antigens. Self-directed immune responses induced/worsened by HERV expression are suspected to participate in both tissue-specific and systemic disorders. A substantial level of mechanistic investigation is needed to better delineate the impact of HERV expression in diseases in general, and in inflammation and autoimmunity in particular., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Malignant pleural effusion (MPE) is one of the most difficult complications of cancer to cure, usually indicating poor prognosis in late-stage cancer patients. Due to the presence of a large number of tumor-associated immune cells with the tumor promoting phenotype in MPE and pleural tumors, current clinical therapy offers limited effectiveness. Here, a mild magnetothermal regulation strategy is proposed based on a magnetic nanocatlytic nanoplatform ZCMF@PEG-AF (ZCMF-AF) constructed by surface-modifying anti-F4/80 antibody (AF) on ZnCoFe 2 O 4 @ZnMnFe 2 O 4 magnetic nanoparticles (ZCMF) to target and polarize tumor-associated macrophages. Under alternating magnetic field-induced hyperthermia (41-42 °C), ZCMF-AF exhibits in situ nanocatalytic production of hydroxyl radicals via released iron ions under acidic cellular environment, which induces repolarization from the immunosuppressed M2 phenotype to the M1 phenotype. More importantly, the tumor cell damage induced by M1 macrophages and magnetic hyperthermia promote the maturation of dendritic cells, which subsequently awakens cytotoxic T lymphocytes to combat tumor cells. The integrated innate and adaptive immunity activations based on ZCMF-AF nano-immunomedicine through intrapleural administration elicit substantially regulated immune microenvironment of MPE and pleural tumors. Moreover, the interpleural magnetic nanoparticle-based immunotherapy effectively reduced the MPE volume and inhibited tumor growth in the pleural cavity, significantly prolonging the survival of the MPE-bearing mice., (© 2024 Wiley‐VCH GmbH.)

The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.

Numerous benefits of nanotechnology are available in many scientific domains. In this sense, nanoparticles serve as the fundamental foundation of nanotechnology. Recent developments in nanotechnology have demonstrated that nanoparticles have enormous promise for use in almost every field of life sciences. Nanoscience and nanotechnology use the distinctive characteristics of tiny nanoparticles (NPs) for various purposes in electronics, fabrics, cosmetics, biopharmaceutical industries, and medicines. The exclusive physical, chemical, and biological characteristics of nanoparticles prompt different immune responses in the body. Nanoparticles are believed to have strong potential for the development of advanced adjuvants, cytokines, vaccines, drugs, immunotherapies, and theranostic applications for the treatment of targeted bacterial, fungal, viral, and allergic diseases and removal of the tumor with minimal toxicity as compared to macro and microstructures. This review highlights the medical and non-medical applications with a detailed discussion on enhanced and targeted natural and acquired immunity against pathogens provoked by nanoparticles. The immunological aspects of the nanotechnology field are beyond the scope of this Review. However, we provide updated data that will explore novel theragnostic immunological applications of nanotechnology for better and immediate treatment.

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]

Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of •NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19.