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Background Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and in viral infections of the central nervous system is increasing and specific inhibitors are available as therapeutic options. Methods In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to noninflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using postmortem brain tissue samples. Results We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent, and C3 complement deposits were detected in postmortem brain sections. Intrathecal complement levels were negatively correlated with survival. Conclusions Further investigations are warranted to clarify whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis. [ABSTRACT FROM AUTHOR]

Malaria is one of the most infectious disease that affects lives of million people throughout the world. Recently, there are several reports which indicate Plasmodium vivax (P. vivax) causing severe disease in infected patients from different parts of the world. For P. vivax disease severity, the data related to immunological and inflammatory status in human host is very limited. In the present study clinical parameters, cytokine profile and integrin gene were analyzed in P. vivax clinical patients. A total of 169 P. vivax samples were collected and categorized into severe vivax malaria (SVM; n = 106) and non-severe vivax malaria (NSVM; n = 63) according to WHO severity criteria. We measured host biomarker levels of interferon (IFN-γ), superoxide dismutase (SOD-1), interleukins viz. (IL-6, IL-10), and tumor necrosis factor (TNF-α) in patient plasma samples by ELISA for pro- and anti-inflammatory cytokines in severe malaria. Host integrin gene was genotyped using PCR assay. In our study, thrombocytopenia and anemia were major symptoms in severe P. vivax patients. In analyzed SVM and NSVM groups a significant increase in cytokine levels (IL-10, IL-6, and TNF-α) and anti-oxidant enzyme SOD-1 was found. Our study results also showed a higher pro-inflammatory (TNF-α, IL-6 and IFN-γ) to anti-inflammatory (IL-10) cytokine ratio in severe vivax patients. Integrin gene showed no mutation with respect to thrombocytopenic patients among clinically defined groups. It was observed that severe vivax cases had increased cytokine levels irrespective of age and sex of the patients along with thrombocytopenia and other clinical manifestations. The results of current findings could serve as baseline data for evaluating severe malaria parameters during P. vivax infections and will help in developing an effective biomarker for diagnosis. [ABSTRACT FROM AUTHOR]

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (P. falciparum) infection, with complex pathogenesis involving multiple factors, including the host's immunological response. T lymphocytes, specifically CD4+ T helper cells and CD8+ cytotoxic T cells, are crucial in controlling parasite growth and activating cells for parasite clearance via cytokine secretion. Contrary to this, reports also suggest the pathogenic nature of T lymphocytes as they are often involved in disease progression and severity. CD8+ cytotoxic T cells migrate to the host's brain vasculature, disrupting the blood-brain barrier and causing neurological manifestations. CD4+ T helper cells on the other hand play a variety of functions as they differentiate into different subtypes which may function as pro-inflammatory or anti-inflammatory. The excessive pro-inflammatory response in CM can lead to multi-organ failure, necessitating a check mechanism to maintain immune homeostasis. This is achieved by regulatory T cells and their characteristic cytokines, which counterbalance the pro-inflammatory immune response. Maintaining a critical balance between pro and anti-inflammatory responses is crucial for determining disease outcomes in CM. A slight change in this balance may contribute to a disease severity owing to an extreme inflammatory response or unrestricted parasite growth, a potential target for designing immunotherapeutic treatment approaches. The review briefly discusses the pathogenesis of CM and various mechanisms responsible for the disruption of the blood-brain barrier. It also highlights the role of different T cell subsets during infection and emphasizes the importance of balance between pro and anti-inflammatory T cells that ultimately decides the outcome of the disease. SUMMARY: CM is potentially fatal complication of P. falciparum infection that presents with high mortality and morbidity. Vaccines are extensively being developed against the Plasmodium parasite but very few of them are effective. Artemisinin Combination Therapy (ACT) is a major treatment for malaria, but its effectiveness is declining due to Plasmodium sp. developing resistance to it, necessitating the need for development of new drugs and treatments. During infection, the parasite is responsible for causing infected red blood cell (RBC) sequestration and cytoadherence in brain vasculature and extreme pro-inflammatory response that ultimately causes endothelial dysfunction and bloodbrain barrier (BBB) disruption. The host initiates a pro-inflammatory response against the parasite which includes activation of cells of both innate and adaptive immune response. These cells control the parasite growth and aid in parasite clearance from host's body. The inflammatory response generally targets foreign pathogens and provides protection against possible infection but can also cause harm to the self when left unchecked. It has been reported that activated immune cells, mainly T-lymphocytes often migrate to brain vasculature and ultimately results in neuronal damage characteristic CM. To counteract the overwhelming pro-inflammatory response, the host immune system deploys an anti-inflammatory response, which often involves regulatory cells and cytokines that help the body maintain immunological homeostasis. The review briefly highlights the necessity of balancing the pro- and anti-inflammatory responses for successful parasite clearance without the deleterious effects to the host that might increase disease severity in CM. [ABSTRACT FROM AUTHOR]

A wide variety of inflammatory mediators, mainly cytokines and chemokines, are induced during SARS CoV‐2 infection. Among these proinflammatory mediators, chemokines tend to play a pivotal role in virus‐mediated immunopathology. The C‐C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein‐1 (MCP‐1) is a potent proinflammatory cytokine and strong chemoattractant of monocytes, macrophages and CD4+ T cells bearing C‐C chemokine receptor type‐2 (CCR2). Besides controlling immune cell trafficking, CCL2 is also involved in multiple pathophysiological processes including systemic hyperinflammation associated cytokine release syndrome (CRS), organ fibrosis and blood coagulation. These pathological features are commonly manifested in severe and fatal cases of COVID‐19. Given the crucial role of CCL2 in COVID‐19 pathogenesis, the CCL2:CCR2 axis may constitute a potential therapeutic target to control virus‐induced hyperinflammation and multi‐organ dysfunction. Herein we describe recent advances on elucidating the role of CCL2 in COVID‐19 pathogenesis, prognosis, and a potential target of anti‐inflammatory interventions. [ABSTRACT FROM AUTHOR]

Gyrovirus (GyV) is small, single-stranded circular DNA viruses that has recently been assigned to the family Anelloviridae. In the last decade, many GyVs that have an apparent pan-tropism at the host level were identified by high-throughput sequencing (HTS) technology. As of now, they have achieved global distribution. Several species of GyVs have been demonstrated to be pathogenic to poultry, particularly chicken anemia virus (CAV), causing significant economic losses to the global poultry industry. Although GyVs are highly prevalent in various birds worldwide, their direct involvement in the etiology of specific diseases and the reasons for their ubiquity and host diversity are not fully understood. This review summarizes current knowledge about GyVs, with a major emphasis on their morphofunctional properties, epidemiological characteristics, genetic evolution, pathogenicity, and immunopathogenesis. Additionally, the association between GyVs and various diseases, as well as its potential impact on the poultry industry, have been discussed. Future prevention and control strategies have also been explored. These insights underscore the importance of conducting research to establish a virus culture system, optimize surveillance, and develop vaccines for GyVs. [ABSTRACT FROM AUTHOR]

The adverse outcomes of fungal infection in mammalian hosts depend on the complex interactions between the host immune system and pathogen virulenceassociated traits. The main clinical problems arise when the host response is either too weak to effectively eliminate the pathogen or overly aggressive, resulting in host tissue damage rather than protection. This article will highlight current knowledge regarding the virulence attributions and mechanisms involved in the dual-sided role of the host immune system in the immunopathogenesis of the thermally dimorphic fungus Talaromyces marneffei through the lens of the damage response framework (DRF) of microbial pathogenesis model. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by inflammatory back pain and bony fusion of vertebral joints. Genetic associations and environmental factors have been proposed to explain the immunopathogenesis of AS. In the past few years, there have been major advances in understanding T cell dysfunction in AS. Clinically, targeting interleukin-17A, a major cytokine secreted by T helper 17 cells, has been approved for treating patients with active AS. Non-coding RNAs (ncRNAs) are RNA transcripts that do not translate into proteins. The ncRNAs regulate both innate and adaptive immunity and participate in the pathogenesis of autoimmune diseases, including AS. The main purpose of this article is to review the up-to-date studies investigating the aberrant expression of ncRNAs in T cells from patients with AS and to summarize their roles in its pathogenesis. After searching PubMed for studies published between January 2013 and June 2024, nine studies investigating the expression of ncRNAs in AS T cells were included. We found that aberrantly expressed ncRNAs in AS T cells could cause abnormal cytokine release, cell signaling abnormalities, and dysregulated cell proliferation and death, which contribute to the immunopathogenesis of AS. We discussed some limitations of these studies and suggested several research fields for further investigation. [ABSTRACT FROM AUTHOR]

Hepatitis B is an infectious disease resulting from infection with the hepatitis B virus. Chronic hepatitis B (CHB) is characterized by prolonged inflammation in the liver, the development of fibrosis, liver cirrhosis and hepatocellular carcinoma. Factors of the immune system play a critical role in the pathogenesis of CHB. Thanks to chemokines, immune cells migrate to the site of inflammation to implement their effector functions. The CX3CL1/Fractalkine chemokine is the only member of the CX3C family of chemokines with unique structural and functional properties. Its receptor CX3CR1 is expressed mainly on the surface of cytotoxic effector lymphocytes such as NK cells, TNK and cytotoxic T lymphocytes. The purpose of our study was to analyze the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB and the analysis of this chemokine with liver fibrosis. The concentration of CX3CL1/Fractalkine was determined in the blood plasma of patients with CHB using a multiplex assay based on xMAP technology. Blood plasma from patients with chronic viral hepatitis C (CHC) and autoimmune liver diseases (AILD) was used as a comparison group. The control group consisted of healthy individuals. For statistical analysis of data, nonparametric statistics methods were used: Kruskal–Wallis test, Spearman correlation coefficient ROC-analysis. It was shown a reduced level of CX3CL1/Fractalkine in patients with CHB compared with the control group (p = 0.0003) and with the comparison groups of CHC (p 0.0001) and AILD (p = 0.0005). A reduced concentration of CX3CL1/Fractalkine was shown in the blood plasma of CHB patients with initial fibrosis (p = 0.0092) and severe fibrosis/cirrhosis (p = 0.0009), while in patients with severe fibrosis/cirrhosis, a significantly reduced level of this chemokine was established compared with the initial degree of liver fibrosis (p = 0.0081). Correlation analysis revealed a highly significant inverse relationship between the severity of liver fibrosis and the content of CX3CL1/Fractalkine in the blood plasma of patients with CHB (Spearman r = –0.33; p = 0.02). Thus, the chemokine CX3CL1/Fractalkine is included in the immunopathogenesis of CHB; its reduced content is characteristic only of CHB and does not change in other chronic liver diseases. It is involved in the processes of liver fibrosis during infection with the hepatitis B virus. The concentration of the chemokine CX3CL1/Fractalkine depends on the stage of liver fibrosis in CHB, and a decrease in the level of CX3CL1/Fractalkine in the blood plasma can serve as a negative factor in the development of CHB.

Relevance. Hemorrhagic fever with renal syndrome (HFRS) is a natural focal viral infection with a high probability of severe course, the possibility of death, a long recovery period after infection, low effectiveness of therapy and vaccine prevention. In the Russian Federation, HFRS is most often caused by the Puumala orthohantavirus. The aim of the study — to evaluate the immunophenotypic composition of lymphocytes and cytokine profile in the blood of patients with hemorrhagic feverwith renal syndrome in comparison with acute respiratory viral infections and with the prospect of developing immunological criteria for early diagnosis of HFRS. Matherials and Methods. There were examined the blood of 24 patients with a verified diagnosis of HFRS who were hospitalized in the infectious diseases department of the Samara Medical University Clinics and admitted in the first days of the disease, 18 patients with acute respiratory viral infections of established etiology, as well as 15 healthy people. Results and Discussion. Analysis of the results of lymphocyte phenotyping and cytokine levels in the blood revealed that the percentage of B lymphocytes in the blood was 12.6 %, cytotoxic CD8+ T lymphocytes expressing the activating lectin receptor NKG2D (CD3+CD8+CD314+), 25 %, regulatory T cells with CD3+CD4+FoxP3+ phenotypes 7.8 % and CD3+CD8+FoxP3+ 9.5 %, as well as IL-6 24 pg/ml, TNFß 55 pg/ml, IL-10 11.3 pg/ml with high diagnostic significance, judging by the results of ROC analysis, indicates in favor of GLPS, but not ARVI. Conclusion. The results obtained can be used as criteria for early immunodiagnosis of HFRS. The development of a new hypothesis on the mechanism of CD8+ immunological memory formation may contribute to the discovery of new potential targets for HFRS immunotherapy and the creation of new principles for the production of vaccine preparations for the prevention of this disease.

Aim. To develop and evaluate the effectiveness of complex therapy of vulvar lichen sclerosus (VLS), considering the clinical and immunological variant (CIV) of the disease. Materials and methods. A randomized prospective study included 292 patients 20-70 years old with different CIVs of the VLS course: atrophic (n=101), sclerosing (n=154), scleroatrophic (n=37), as well as 35 females with VLS in the comparison group of the same age category. Based on the clinical, immunological, and morphological features of the VLS course, a complex anti-relapse therapy was developed, the effectiveness of which was evaluated after a year of follow-up in comparison with the standard of care (SoC) of patients (from the comparison group) based on the number of disease relapses and the results of the Vulvar Quality of Life Index Questionnaire (VQLI) survey of women with vulvar diseases. Results. In patients with the sclerosing variant of VLS, short courses of topical glucocorticoids during exacerbations are justified; in patients with the scleroatrophic variant – topical calcineurin inhibitors, in the atrophic variant – a protein-peptide complex from porcine blood leukocytes (vaginal suppositories and cream-balsam with lanolin) containing interleukin-1, 6, tumor necrosis factor α, transforming growth factor, macrophage migration inhibitory factor. Patients with any variant of VLS are instructed to follow household and hygienic recommendations, use emollients daily, take prophylactic doses of vitamins A, E, and D to correct its deficiency or insufficiency, as well as use local enzyme therapy, as indicated, aimed at preventing or treatment of cicatricial changes. Local estrogens were prescribed only to women with genitourinary menopausal syndrome in the peri- and postmenopausal period. The developed complex anti-relapse therapy of VLS showed greater clinical efficacy compared to SoC: 3.7-fold decrease in episodes of disease exacerbation, as well as a significant (p=0.001) 1.3-fold decrease in the negative effect of VLS on the QoL of patients in the main clinical group (15.4 points according to the VQLI assessment – a mild effect on QoL) compared to SoC with the average score of 27.6, which corresponded to a strong negative effect of the disease on QoL. Conclusion. The results of the study support the distinction of VLS CIVs and the need to consider their features when choosing an effective therapy for the disease. Properly selected complex, supportive therapy of VLS can significantly increase the QoL of patients, minimize the number of relapses, and prevent the development of complications, including, probably, the risk of malignant transformation.

Abstract Background The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes. Methods We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics. Results We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts. Conclusions This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes. Graphical Abstract

Helicobacter pylori infection is a well-established risk factor for the development of gastric cancer (GC). Understanding the immunopathogenesis underlying this association is crucial for developing effective preventive and therapeutic strategies. This narrative review comprehensively explores the immunopathogenesis of H. pylori-induced GC by delving into several key aspects, emphasizing the pivotal roles played by H. pylori virulence factors, including cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA), blood group antigen-binding adhesin (babA), and sialic acid binding adhesin (sabA). Moreover, the review focuses on the role of toll-like receptors (TLRs) and cytokines in the complex interplay between chronic infection and gastric carcinogenesis. Finally, the study examines the association between H. pylori evasion of the innate and adaptive immune response and development of GC. A comprehensive understanding of the immunopathogenesis of H. pylori-induced GC is essential for designing targeted interventions to prevent and manage this disease. Further research is warranted to elucidate the intricate immune responses involved and identify potential therapeutic targets to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Chronic inflammation has long been considered the characteristic feature of type II diabetes mellitus (T2DM) Immunopathogenesis. Pro-inflammatory cytokines are considered the central drivers of the inflammatory cascade leading to β-cell dysfunction and insulin resistance (IR), two major pathologic events contributing to T2DM. Analyzing the cytokine profile of T2DM patients has also introduced interleukin-17 (IL-17) as an upstream regulator of inflammation, regarding its role in inducing the nuclear factor-kappa B (NF-κB) pathway. In diabetic tissues, IL-17 induces the expression of inflammatory cytokines and chemokines. Hence, IL-17 can deteriorate insulin signaling and β-cell function by activating the JNK pathway and inducing infiltration of neutrophils into pancreatic islets, respectively. Additionally, higher levels of IL-17 expression in patients with diabetic complications compared to non-complicated individuals have also proposed a role for IL-17 in T2DM complications. Here, we highlight the role of IL-17 in the Immunopathogenesis of T2DM and corresponding pathways, recent advances in preclinical and clinical studies targeting IL-17 in T2DM, and corresponding challenges and possible solutions. • T2DM is an obesity-induced chronic inflammatory disease driven by proinflammatory cytokines and chemokines, such as IL-7, IL1-β, IL-6, TNF-α, IL-17, and C-reactive protein (CRP). • IL17 is a potent proinflammatory cytokine produced by T-helper 17 cells and adipose tissue. • Altered production of IL17, mainly through activation of nuclear factor-kappa B (NF-κB), leads to inflammation-induced insulin resistance and β-cell dysfunction, the two main immunopathogenic pathways leading to T2DM. • Studies have shown conflicting results regarding the involvement of IL17 in diabetic nephropathy, which is still under exploration. Diabetic retinopathy, however, is considered to be the result of BRB destruction and activation of Müller cells. • The exact mechanism involved in diabetic neuropathy is not recognized yet, but it may be related to the dysregulating Schwan cell-mediated myelination and postsynaptic GABA channel suppression. • IL17 is considered a double-edged cytokine in inflammatory states in the peripheral vasculature which may be both a risk or a protective factor in cardiovascular complications of T2DM. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis. [ABSTRACT FROM AUTHOR]

Background: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. Result: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. Conclusion: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts. [ABSTRACT FROM AUTHOR]

Background: The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes. Methods: We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics. Results: We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts. Conclusions: This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes. [ABSTRACT FROM AUTHOR]

Type I interferons (IFN-Is) are important players in the immunopathogenesis of systemic lupus erythematosus (SLE). Pathogenic events in patients with SLE are potent triggers of IFN-I induction, yet IFN-I may induce or initiate the immunopathogenesis leading to these events. Because blocking IFN-I is effective in some clinical manifestations of SLE patients, concerns about the efficacy of anti-IFN-I therapy in patients with lupus nephritis remain. Tissues from kidney biopsies of patients with lupus nephritis revealed infiltration of various immune cells and activation of inflammatory signals; however, their correlation with renal damage is not clear, which raises serious concerns about how critical the role of IFN-I is among the potential contributors to the pathogenesis of lupus nephritis. This review addresses several issues related to the roles of IFN-I in SLE, especially in lupus nephritis, including (1) the contribution of IFN-I to the development and immunopathogenesis of SLE; (2) evidence supporting the association of IFN-I with lupus nephritis; (3) therapies targeting IFN-I and IFN-I downstream signaling molecules in SLE and lupus nephritis; (4) findings challenging the therapeutic benefits of anti-IFN-I in lupus nephritis; and (5) a perspective associated with anti-IFN-I biologics for lupus nephritis treatment. In addition to providing clear pictures of the roles of IFN-I in SLE, especially in lupus nephritis, this review addresses the lately published observations and clinical trials on this topic.

The adverse outcomes of fungal infection in mammalian hosts depend on the complex interactions between the host immune system and pathogen virulence-associated traits. The main clinical problems arise when the host response is either too weak to effectively eliminate the pathogen or overly aggressive, resulting in host tissue damage rather than protection. This article will highlight current knowledge regarding the virulence attributions and mechanisms involved in the dual-sided role of the host immune system in the immunopathogenesis of the thermally dimorphic fungus Talaromyces marneffei through the lens of the damage response framework (DRF) of microbial pathogenesis model.

The aim of the review is to give a brief characteristic of cell cultures obtained from mammalian tissues and to consider the current possibilities and prospects for their use in virology. The analysis of the literature data presented in the main databases, such as Web of Science, PubMed, Scopus, Elsevier, Google Scholar and RSCI (as of July 2023), indicates that various types of cell cultures are currently used in virological studies. The use of cell culture has a number of advantages over other in vitro and in vivo methods of virological research. The review provides numerous examples on the development of new methods of obtaining cell cultures for the cultivation of viruses. Among them are sensitive and reporter cell systems, the design of which can be a promising tool for diagnostics of existing and new unknown viral infections. Cell cultures are characterized as potential in vitro models in virology for developing new diagnostic test-systems and antiviral drugs. An important area of cell cultures application is their use as a substrate for the production of culture-derived vaccines. Another aspect of the cell cultures application is also highlighted, such as the study of the effect of the viruses on the host immune system or the mechanisms of immunopathogenesis of viral infections. It is concluded that the use of cell cultures remains currently and in the near future one of the most important methods in practical virology and in scientific research.

Abstract Communications between immune cells are essential to ensure appropriate coordination of their activities. Here, we observed the infiltration of activated macrophages into the joint-footpads of chikungunya virus (CHIKV)-infected animals. Large numbers of CD64+MHCII+ and CD64+MHCII- macrophages were present in the joint-footpad, preceded by the recruitment of their CD11b+Ly6C+ inflammatory monocyte precursors. Recruitment and differentiation of these myeloid subsets were dependent on CD4+ T cells and GM-CSF. Transcriptomic and gene ontology analyses of CD64+MHCII+ and CD64+MHCII- macrophages revealed 89 differentially expressed genes, including genes involved in T cell proliferation and differentiation pathways. Depletion of phagocytes, including CD64+MHCII+ macrophages, from CHIKV-infected mice reduced disease pathology, demonstrating that these cells play a pro-inflammatory role in CHIKV infection. Together, these results highlight the synergistic dynamics of immune cell crosstalk in driving CHIKV immunopathogenesis. This study provides new insights in the disease mechanism and offers opportunities for development of novel anti-CHIKV therapeutics.

Objectives: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. Methods: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings ‘HIVE’, ‘SD’, and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. Results: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. Conclusion: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.

Communications between immune cells are essential to ensure appropriate coordination of their activities. Here, we observed the infiltration of activated macrophages into the joint-footpads of chikungunya virus (CHIKV)-infected animals. Large numbers of CD64+MHCII+ and CD64+MHCII- macrophages were present in the joint-footpad, preceded by the recruitment of their CD11b+Ly6C+ inflammatory monocyte precursors. Recruitment and differentiation of these myeloid subsets were dependent on CD4+ T cells and GM-CSF. Transcriptomic and gene ontology analyses of CD64+MHCII+ and CD64+MHCII- macrophages revealed 89 differentially expressed genes, including genes involved in T cell proliferation and differentiation pathways. Depletion of phagocytes, including CD64+MHCII+ macrophages, from CHIKV-infected mice reduced disease pathology, demonstrating that these cells play a pro-inflammatory role in CHIKV infection. Together, these results highlight the synergistic dynamics of immune cell crosstalk in driving CHIKV immunopathogenesis. This study provides new insights in the disease mechanism and offers opportunities for development of novel anti-CHIKV therapeutics. Synopsis: Activated CD64+MHCII+ macrophages are present in the joint-footpad during CHIKV infection and participate in a pathogenic immune crosstalk with CD4+ T cells to drive immunopathogenesis. CD64+MHCII+ macrophages could be an alternative host-directed therapeutic target against CHIKV infection. Mass cytometry reveals the presence of CD64+MHCII+ macrophages in the CHIKV-infected joint-footpad. IFNγ and GM-CSF secreted by CD4+ T cells are two mediators capable of regulating the levels of CD64+MHCII+ macrophages in CHIKV-infected joints. In vivo depletion of GM-CSF reduces CHIKV disease severity. CD64+MHCII+ macrophages are involved in multiple T-cell-related pathways as revealed by RNAseq analyses. CD64+MHCII+ macrophages are potential novel targets for the future development of anti-CHIKV therapeutics. Activated CD64+MHCII+ macrophages are present in the joint-footpad during CHIKV infection and participate in a pathogenic immune crosstalk with CD4+ T cells to drive immunopathogenesis. CD64+MHCII+ macrophages could be an alternative host-directed therapeutic target against CHIKV infection. [ABSTRACT FROM AUTHOR]

Scabies is an itchy skin disease caused by the burrowing mite Sarcoptes scabiei. During their lifespan, the female mites invade the stratum corneum and create tunnels, in which they reside, move, feed, deposit fecal pellets, and lay eggs. Recently, scabies was included in the World Health Organization roadmap for neglected tropical diseases 2021–2030. This review attempts to summarize our knowledge about the mite's biology and the disease pathogenesis, pathological changes, and complications. Generally, the host–parasite interaction in scabies is highly complex and involves different mechanisms, some of which are yet largely unknown. Elucidation of the nature of such interaction as well as the underlying mechanisms could allow a better understanding of the mite's biology and the development of novel diagnostic and therapeutic options for scabies control programs. Moreover, identification of the molecular basis of such interaction could unveil novel targets for acaricidal agents and vaccines. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2  weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5  days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV. [ABSTRACT FROM AUTHOR]

• Slim disease (SD) became recognised as an AIDS-defining illness in East African patients in 1985. • HIV enteropathy is characterised by villous atrophy, crypt cell hyperplasia and presents as SD. • Persistent diarrhoea, wasting and malabsorption are major manifestations of SD. • Gut clusters of differentiation 4+ T helper 17+ and intra-epithelial γδ T cells are important in HIV enteropathy pathogenesis. • Highly active antiretroviral therapy leads to regeneration of mucosal epithelium. Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is a well-established risk factor for the development of gastric cancer (GC). Understanding the immunopathogenesis underlying this association is crucial for developing effective preventive and therapeutic strategies. This narrative review comprehensively explores the immunopathogenesis of H. pylori-induced GC by delving into several key aspects, emphasizing the pivotal roles played by H. pylori virulence factors, including cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA), blood group antigen-binding adhesin (babA), and sialic acid binding adhesin (sabA). Moreover, the review focuses on the role of toll-like receptors (TLRs) and cytokines in the complex interplay between chronic infection and gastric carcinogenesis. Finally, the study examines the association between H. pylori evasion of the innate and adaptive immune response and development of GC. A comprehensive understanding of the immunopathogenesis of H. pylori-induced GC is essential for designing targeted interventions to prevent and manage this disease. Further research is warranted to elucidate the intricate immune responses involved and identify potential therapeutic targets to improve patient outcomes.

Toxoplasma gondii (T. gondii) is a cosmopolitan protozoan parasite in humans and animals. It infects about 30 % of the human population worldwide and causes potentially fatal diseases in immunocompromised hosts and neonates. For this study, five English-language databases (ScienceDirect, ProQuest, Web of Science, PubMed, and Scopus) and the internet search engine Google Scholar were searched. This review was accomplished to draw a global perspective of what is known about the pathogenesis of T. gondii and various factors affecting it. Virulence and immune responses can influence the mechanisms of parasite pathogenesis and these factors are in turn influenced by other factors. In addition to the host's genetic background, the type of Toxoplasma strain, the routes of transmission of infection, the number of passages, and different phases of parasite life affect virulence. The identification of virulence factors of the parasite could provide promising insights into the pathogenesis of this parasite. The results of this study can be an incentive to conduct more intensive research to design and develop new anti-Toxoplasma agents (drugs and vaccines) to treat or prevent this infection. In addition, further studies are needed to better understand the key agents in the pathogenesis of T. gondii.

Introduction: Periodontitis is one of the most prevalent diseases occurring worldwide, and is caused by an imbalance of host immunological defenses and microbiome profile which occurs in the oral cavity. This imbalance leads to irregularity and uncontrolled activities of immune cells, resulting in over-reactivity of periodontopathogens and tissue destruction. To alleviate periodontitis, exact targeting of specific events involving particular cells could be a potential application of immunomodulatory agents. Phytochemical drug development targeting specific immunopathogenesis events could be a promising complementary, alternative approach to periodontal therapy. Objectives: This review aimed to explore various events involving a variety of cells in the immunopathogenesis of periodontitis in order to determine potential specific immunomodulation targets for future development of effective phytochemical drugs. Results: Immunopathogenesis of periodontitis contributes significantly to the disease onset and resolution. Various events occur during the disease development, which involve a variety of immune cells and mediators. Among these, neutrophils, cytokines and lymphocytes, especially Th17 cells, were reported to be the most relevant components in the disease pathogenesis. These components affect the initial responses to periodontopathogens, inhibit oxidative stress formation, control intercellular communication to enhance inflammation, and promote effector cells’ migration to induce alveolar bone resorption. Several phytochemical drugs were developed to cure periodontitis, however, the development of phytochemical immunomodulatory drugs to target specific events has not been realized. Conclusion: This review concluded that development of phytochemical immunomodulatory drugs to target particular events generated by neutrophils, pro-inflammatory cytokines and lymphocytes has tremendous potential to regulate and modulate the immunopathogenesis of periodontitis.

Mycosis fungoides (MF) is the most common subtype of Cutaneous T-Cell Lymphoma (CTCL). Patients with Skin of Color (SOC) may be disproportionately impacted by MF due to delayed diagnoses, limited research, and treatment differences. In this graphical review, we provide an overview of MF immunopathogenesis and demonstrate how it manifests differently in SOC patients. We also provide our hypothesis for why the disease process can result in a myriad of clinical presentations in SOC patients. Last, we provide a summary of current treatment options, highlighting ongoing clinical trials and opportunities to include SOC patients to promote health equity.

Cutaneous T-cell lymphoma (CTCL) serves as an umbrella term for numerous lymphomas that reside in or recirculate through the skin. One such systemic lymphoma is Sézary Syndrome (SS). Although SS is not as common in Skin of Color (SOC), minority patients presenting with the condition do have a different presentation than their White counterparts. In this graphical review, we provide an overview of SS immunopathogenesis and varying presentations. Additionally, a summary of current treatment options is provided, highlighting ongoing clinical trials and opportunities to include SOC patients to promote health equity. SOC patients often have poorer prognosis due to biological differences and health disparities resulting in delayed diagnosis. This exemplifies the potential advantages and promising solutions of precision medicine implementation. To this end, the impact and benefits of precision medicine are summarized.

SARS-CoV-2, responsible for COVID-19, shares 79% and 50% of its identity with SARS-CoV-1 and MERS-CoV, respectively. It uses the same main cell attachment and entry receptor as SARS-CoV-1, which is the ACE-2 receptor. However, key residues in the receptor-binding domain of its S-protein seem to give it a stronger affinity for the receptor and a better ability to hide from the host immune system. Like SARS-CoV-1 and MERS-CoV, cytokine storms in critically ill COVID-19 patients cause ARDS, neurological pathology, multiorgan failure, and increased death. Though many issues remain, the global research effort and lessons from SARS-CoV-1 and MERS-CoV are hopeful. The emergence of novel SARS-CoV-2 variants and subvariants raised serious concerns among the scientific community amid the emergence of other viral diseases like monkeypox and Marburg virus, which are major concerns for healthcare settings worldwide. Hence, an updated review on the comparative analysis of various coronaviruses (CoVs) has been developed, which highlights the evolution of CoVs and their repercussions.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by inflammatory back pain and bony fusion of vertebral joints. Genetic associations and environmental factors have been proposed to explain the immunopathogenesis of AS. In the past few years, there have been major advances in understanding T cell dysfunction in AS. Clinically, targeting interleukin-17A, a major cytokine secreted by T helper 17 cells, has been approved for treating patients with active AS. Non-coding RNAs (ncRNAs) are RNA transcripts that do not translate into proteins. The ncRNAs regulate both innate and adaptive immunity and participate in the pathogenesis of autoimmune diseases, including AS. The main purpose of this article is to review the up-to-date studies investigating the aberrant expression of ncRNAs in T cells from patients with AS and to summarize their roles in its pathogenesis. After searching PubMed for studies published between January 2013 and June 2024, nine studies investigating the expression of ncRNAs in AS T cells were included. We found that aberrantly expressed ncRNAs in AS T cells could cause abnormal cytokine release, cell signaling abnormalities, and dysregulated cell proliferation and death, which contribute to the immunopathogenesis of AS. We discussed some limitations of these studies and suggested several research fields for further investigation.

Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B-cell hyperactivation are the two salient pathologic features in Sjögren's syndrome. Increasing evidence indicates that salivary gland epithelial cells act as a key regulator in the pathogenesis of Sjögren's syndrome, as revealed by the dysregulated innate immune signaling pathways in salivary gland epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells. In addition, salivary gland epithelial cells can regulate adaptive immune responses as nonprofessional antigen-presenting cells and promote the activation and differentiation of infiltrated immune cells. Moreover, the local inflammatory milieu can modulate the survival of salivary gland epithelial cells, leading to enhanced apoptosis and pyroptosis with the release of intracellular autoantigens, which further contributes to SG autoimmune inflammation and tissue destruction in Sjögren's syndrome. Herein, we reviewed recent advances in elucidating the role of salivary gland epithelial cells in the pathogenesis of Sjögren's syndrome, which may provide rationales for potential therapeutic targeting of salivary gland epithelial cells to alleviate salivary gland dysfunction alongside treatments with immunosuppressive reagents in Sjögren's syndrome. [ABSTRACT FROM AUTHOR]

Behçet's syndrome is a recurring inflammatory multiorgan disorder affecting the skin, mucosa, eyes, joints, stomach, and central nervous system. Behçet's syndrome epidemiology varies greatly among populations (0.64–420/100,000), and Behçet's syndrome has gained increasing international acclaim in the recent 50 years due to raising awareness of the syndrome, although it is rare in most population. In addition to the unclear etiology of the syndrome, the diagnosis of Behçet's syndrome is complicated by a vague clinical presentation, phenotypic heterogeneity and/or incomplete representation, and the lack of any specific laboratory, radiographic, or histological findings. There exists a dire need to elucidate factors that contribute to disease pathogenesis and/or are associated with clinical features of Behçet's syndrome and the classification of different forms of the syndrome. The identification of such molecular, cellular, and/or clinical factors are crucial for timely diagnosis and efficacious management of Behçet's syndrome. We discuss recent advances in the clinical diagnosis of Behçet's syndrome and related contributions of genetics, epigenetics, microbiome, inflammasomes, and autoantibodies to the improved diagnosis, management, and understanding of Behçet's syndrome. [ABSTRACT FROM AUTHOR]

Th17 cells which are crucial for host immunity have been demonstrated to increase HBV infection. However, the mechanism of the Th17 cell increase is unknown. Hence, the mechanism of Th17 cell enhancement is important to provide a theoretical foundation for chronic hepatitis B immunotherapy. This study included 15 instances in the healthy control (HC) and 15 cohorts in the chronic hepatitis B (CHB). Their CD4+T cells were isolated from their peripheral blood and then subjected to RNA transcriptome sequencing. Then, to identify target genes linked to Th17‐cell differentiation, DEGs associated with CHB were convergent with the Th17‐cell‐associated genes from the KEGG database. Hub genes of DEG and target genes linked to Th17 cells were analysed for correlation. The AhR‐related genes were located using the GeneMANIA database. To analyse the function of the genes, GO and KEGG pathways were employed. Protein–protein interaction network analysis employed the Metascape, STRING and Cytoscape databases. Finally, Western blotting and RT‐qPCR were used to validate AhR. A total of 348 differential genes were identified in CHB patients. CytoHubba was used for screening five hub genes associated with CHB: CXCL10, RACGAP1, TPX2, FN1 and GZMA. This study aimed to determine the mechanism of elevated Th17 cells in CHB. As a result, further investigation using the convergence of DGEs and Th17 cell‐related genes identified three target genes: AhR, HLA‐DQA1 and HLA‐DQB1, all of which were elevated in CHB. The three genes were primarily involved in immune response‐related processes, according to the GO enrichment analysis. Correlation analysis of CXCL10, RACGAP1, TPX2, FN1 and GZMA genes with AhR, HLA‐DQA1 and HLA‐DQB1 revealed that AhR was positively associated with CXCL10 and GZMA genes, which best respond to the severity of CHB disease. Combined with the role of AhR in Th17 cell differentiation, the genes AhR was chosen for confirmation by RT‐qPCR and WB in this study. The results showed that the CHB group had higher expression levels of AhR at both RT‐qPCR and WB levels. Furthermore, this study's findings revealed that AhR may contribute to the development of CHB by affecting the differentiation of Th17 cells. [ABSTRACT FROM AUTHOR]

Periodontitis is one of the most prevalent diseases occurring worldwide, and is caused by an imbalance of host immunological defenses and microbiome profile which occurs in the oral cavity. This imbalance leads to irregularity and uncontrolled activities of immune cells, resulting in over-reactivity of periodontopathogens and tissue destruction. To alleviate periodontitis, exact targeting of specific events involving particular cells could be a potential application of immunomodulatory agents. Phytochemical drug development targeting specific immunopathogenesis events could be a promising complementary, alternative approach to periodontal therapy. This review aimed to explore various events involving a variety of cells in the immunopathogenesis of periodontitis in order to determine potential specific immunomodulation targets for future development of effective phytochemical drugs. Immunopathogenesis of periodontitis contributes significantly to the disease onset and resolution. Various events occur during the disease development, which involve a variety of immune cells and mediators. Among these, neutrophils, cytokines and lymphocytes, especially Th17 cells, were reported to be the most relevant components in the disease pathogenesis. These components affect the initial responses to periodontopathogens, inhibit oxidative stress formation, control intercellular communication to enhance inflammation, and promote effector cells' migration to induce alveolar bone resorption. Several phytochemical drugs were developed to cure periodontitis, however, the development of phytochemical immunomodulatory drugs to target specific events has not been realized. This review concluded that development of phytochemical immunomodulatory drugs to target particular events generated by neutrophils, pro-inflammatory cytokines and lymphocytes has tremendous potential to regulate and modulate the immunopathogenesis of periodontitis. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, responsible for COVID-19, shares 79% and 50% of its identity with SARS-CoV-1 and MERS-CoV, respectively. It uses the same main cell attachment and entry receptor as SARS-CoV-1, which is the ACE-2 receptor. However, key residues in the receptor-binding domain of its S-protein seem to give it a stronger affinity for the receptor and a better ability to hide from the host immune system. Like SARS-CoV-1 and MERS-CoV, cytokine storms in critically ill COVID-19 patients cause ARDS, neurological pathology, multiorgan failure, and increased death. Though many issues remain, the global research effort and lessons from SARS-CoV-1 and MERS-CoV are hopeful. The emergence of novel SARS-CoV-2 variants and subvariants raised serious concerns among the scientific community amid the emergence of other viral diseases like monkeypox and Marburg virus, which are major concerns for healthcare settings worldwide. Hence, an updated review on the comparative analysis of various coronaviruses (CoVs) has been developed, which highlights the evolution of CoVs and their repercussions. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.

Aim to evaluate the pathogenetic role of T-lymphocytes carrying the natural killer marker CD56 in hemorrhagic fever with renal syndrome (HFRS). Material and methods. The study group included 65 patients with HFRS receiving the inpatient treatment in the Clinics of SamSMU, and 15 healthy people were chosen for the control group. The following examinations were scheduled for all patients in the different stages of the disease: a clinical blood test, flow cytometry with a given set of monoclonal antibodies, enzyme-linked immunosorbent assay of blood serum to determine the cytokine profile. For statistical analysis we used the SPSS v.23 software. Results. The percentage of CD3+ CD56+ NKT blood content in comparison with those for cells of innate immunity (neutrophil granulocytes, monocytes, natural killers) and lymphocytes of adaptive immune response, as well as the level of cytokines in the blood serum showed that in polyuric and convalescent periods, the number of these cells significantly increases and remains closely embedded in correlations with other components of the immune system. Conclusion. A new hypothesis has been proposed to interpret the role of NKT in the development of the immune response in HFRS.

Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient’s quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.

Plasmodium falciparum and Plasmodium vivax are two major species of malaria that can establish a focus of infection in millions of individuals per year. Principally, this occurs in the tropical and subtropical regions of the world where malaria is endemic due to the ubiquity of the disease vector, the Anopheles mosquitos. Malaria takes the lives of thousands of infected individuals as the progression of disease symptoms having fatal consequences. This disease mainly affects children and pregnant women which poses a great public health concern. It is also a global economic burden from the millions of international dollars are aliquoted for research yearly. This review looks to discuss the pathogenesis of malaria, various host immune responses, the development of clinical immunity in reinfected individuals, and the effects that the presence of one species may have on the pathogenesis and disease outcome of another malarial species in co-infected individuals. Overall, this manuscript aims to provide an understanding of malarial infection and the differing host immune mechanisms of previously exposed individuals compared to those of naïve individuals in environments where malaria is of high prevalence. These highlights indicate a need for further research in order to better understand host-species and species-species interactions so that proper therapeutics and vaccinations may be developed as to not inhibit the beneficial effects species may have on one another in mixed species interactions as well as to aid in the development of clinical immunity.

The aim of the work is to determine the relationship between the levels of cytokines of proinflammatory and anti-inflammatory action during the clinical course of hemorrhagic fever with renal syndrome (HFRS) and the previously described characteristics of the phenotypic composition of blood lymphocytes in disease of various severity. Materials and methods. 65 patients with a serologically verified diagnosis of HFRS were under observation. The control group included 15 conditionally healthy people. Determination of cytokines in the blood of patients with HFRS was carried out by the enzyme immunoassay method at the different stages of the disease. The phenotypic composition of blood lymphocytes was assessed by flow cytofluorimetry. Results. At the different stages of the disease, there was a quantitatively different increase in the content of cytokines in the blood associated with cytotoxic immune reactions (IL-12, IFN, TNFa, TNF), as well as IL-10 and IL-6 correlated with each other in severe cases, against the background of a drop in blood levels of IL-4 and IL-1. In the moderate course of HFRS, correlations of IL-12 and IL-4 with NKG2D+ CTL, the relationship of IL-12 with almost all other cytokines, and the correlation of CD8+ Treg with IL-6 and TNF levels were observed. In severe cases, the formation of a complex that included interconnected IL-6 and IL-10 correlating with the number of NKG2D+ CTL, CD8+ Treg, NKT was noted. Conclusion. The pathogenetically significant mechanism of HFRS is realized with the predominant participation of cytokines of the cellular immune response and IL-6, correlatively associated with NKG2D+ CTL, CD8+ Treg, NKT, which, in case of a favorable outcome, contribute to the active formation of a pool of CD8+ memory cells, disrupted presumably by excessive secretion of IL-10.

Tina Bhutani,1,* Jason E Hawkes2,* 1Psoriasis and Skin Treatment Center, Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA; 2Department of Dermatology, University of California at Davis, Sacramento, CA, USA*Both authors contributed equally to this paperCorrespondence: Dr. Jason E Hawkes, Email hawkes3@gmail.comAbstract: Generalized pustular psoriasis is a rare presentation of psoriatic disease and is characterized by the acute onset of diffuse superficial pustules on the skin. These pustules can often coalesce, forming what’s known as ‘lakes of pus’ that are most often seen on the trunk and on skin folds. GPP flares are often accompanied by systemic symptoms, including fever, malaise, and edema. The interleukin (IL)-36 pathway plays a central role in the development of GPP, although several other genes may be associated. The rarity of GPP makes its diagnosis challenging and it could be mistaken for an infectious condition or other types of pustular psoriasis, including unstable forms of plaque psoriasis that may present with pustules. Performing a thorough skin examination and obtaining a detailed history are vital to exclude these differential diagnoses. Incorrect or late diagnosis, inadequate or delayed treatment, and lack of specialist referrals may contribute to increased disease severity and can have a debilitating impact on patients’ quality of life. In this podcast, two US-based dermatologists discuss the clinical characteristics of GPP, highlight the central role of IL-36 in immunopathogenesis, and share practical approaches to recognizing and diagnosing the disease.Keywords: Diagnosis, generalized pustular psoriasis, genetics, immunopathogenesis, interleukin-36 pathway, quality of life

Behcet's disease (BD) is a chronic multi-systemic disease characterized by relapsing-remitting oral ulcers, genital ulcers, ocular inflammatory involvements, and numerous other systemic features. Ocular involvements are quite common in BD and may cause severe tissue damage and potentially blindness. Even though the pathogenesis of BD remains ambiguous, growing evidences have shown that genetic factors, environmental triggers and immunological abnormalities play significant roles in its development and progression. Novel biotherapies targeting IFN-g, TNF-a and interleukins have been used in recent years. In this review, we mainly pay attention to the ocular involvement of BD, and discuss the current understanding of mechanisms and advances in therapeutic approaches, especially novel biologics. Finally, we discuss the management in patients with pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Kawasaki disease (KD) is an acute febrile illness primarily affecting children and characterized by systemic inflammation and vasculitis that can lead to coronary artery complications. The aim of this study was to gain a comprehensive understanding of immune dysregulation in KD. Methods: To this end, we employed integration of single-cell RNA sequencing (scRNA-Seq) and bulk RNA sequencing (bulk RNA-Seq) data. Furthermore, we conducted flow cytometry analysis for a cohort of 82 KD patients. Results: Our analysis revealed significant heterogeneity within immune cell populations in KD patients, with distinct clusters of T cells, B cells, and natural killer (NK) cells. Importantly, CD4+ naïve T cells in KD patients were found to predominantly differentiate into Treg cells and Th2 cells, potentially playing a role in the excessive inflammation and vascular damage characteristic of the disease. Dysregulated signaling pathways were also identified, including the mTOR signaling pathway, cardiomyopathy pathway, COVID-19 signaling pathway, and pathways involved in bacterial or viral infection. Discussion: These findings provide insights into the immunopathogenesis of KD, emphasizing the importance of immune cell dysregulation and dysregulated signaling pathways. Integration of scRNA-Seq and bulk RNA-Seq data offers a comprehensive view of the molecular and cellular alterations in KD and highlights potential therapeutic targets for further investigation. Validation and functional studies are warranted to elucidate the roles of the identified immune cell types and pathways in KD pathogenesis and to develop targeted interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The first cases of COVID-19 were identified in China in 2019, and the disease subsequently spread rapidly around the world, leading it to be declared a pandemic. The disease affects the lungs through the upper and lower respiratory tracts, and with the development of pneumonia, a clinical picture leading to respiratory failure referred to as cytokine storm occurs as a result of excessive cytokine production associated with an excessive inflammatory immune response. The increase in inflammatory markers is related to acute respiratory distress syndrome, disseminated intravascular coagulation and hypercoagulation. We present here an explanation of cytokine storm and the associated immune damage mechanisms. [ABSTRACT FROM AUTHOR]

Pyroptosis, a form of programmed cell death with a high pro-inflammatory effect, causes cell lysis and leads to the secretion of countless interleukin-1β (IL-1β) and IL-18 cytokines, resulting in a subsequent extreme inflammatory response through the caspase-1-dependent pathway or caspase-1-independent pathway. Adult-onset Still's disease (AOSD) is a systemic inflammatory disease with extensive disease manifestations and severe complications such as macrophage activation syndrome, which is characterized by high-grade inflammation and cytokine storms regulated by IL-1β and IL-18. To date, the pathogenesis of AOSD is unclear, and the available therapy is unsatisfactory. As such, AOSD is still a challenging disease. In addition, the high inflammatory states and the increased expression of multiple pyroptosis markers in AOSD indicate that pyroptosis plays an important role in the pathogenesis of AOSD. Accordingly, this review summarizes the molecular mechanisms of pyroptosis and describes the potential role of pyroptosis in AOSD, the therapeutic practicalities of pyroptosis target drugs in AOSD, and the therapeutic blueprint of other pyroptosis target drugs. [ABSTRACT FROM AUTHOR]