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1.
Sleep Med Clin ; 19(2): 219-228, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692747

ABSTRACT

Obstructive sleep apnea is a prevalent sleep disorder characterized by recurrent episodes of partial or complete upper airway collapse during sleep, leading to disrupted breathing patterns and intermittent hypoxia. OSA results in systemic inflammation but also directly affects the upper and lower airways leading to upregulation of inflammatory pathways and alterations of the local microbiome. These changes result in increased susceptibility to respiratory infections such as influenza, COVID-19, and bacterial pneumonia. This relationship is more complex and bidirectional in individuals with chronic lung disease such as chronic obstructive lung disease, interstitial lung disease and bronchiectasis.


Subject(s)
Respiratory Tract Infections , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/immunology , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , Respiratory Tract Infections/immunology , Respiratory Tract Infections/complications , Disease Susceptibility/immunology , COVID-19/immunology , COVID-19/complications
2.
Immunol Rev ; 323(1): 227-240, 2024 May.
Article in English | MEDLINE | ID: mdl-38577999

ABSTRACT

Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present-day susceptibility to immune-related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation.


Subject(s)
Selection, Genetic , Humans , Animals , Genetic Predisposition to Disease , Immunity/genetics , Genetic Variation , Genetics, Population , Phenotype , Disease Susceptibility/immunology
3.
Viruses ; 14(10)2022 10 19.
Article in English | MEDLINE | ID: mdl-36298850

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi's sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-γ in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-γ-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection.


Subject(s)
B-Lymphocytes , Herpesviridae Infections , Herpesvirus 8, Human , Interferon-gamma , Humans , Acquired Immunodeficiency Syndrome/immunology , B-Lymphocytes/immunology , Castleman Disease/immunology , Cytokines/immunology , Herpesviridae Infections/genetics , Herpesviridae Infections/immunology , Herpesvirus 8, Human/genetics , Herpesvirus 8, Human/immunology , Interferon Regulatory Factor-1/genetics , Interferon Regulatory Factor-1/immunology , Interferon-gamma/immunology , Sarcoma, Kaposi/immunology , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Disease Susceptibility/immunology
4.
Int J Mol Sci ; 23(6)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35328649

ABSTRACT

As the global SARS-CoV-2 pandemic continues to plague healthcare systems, it has become clear that opportunistic pathogens cause a considerable proportion of SARS-CoV-2-associated mortality and morbidity cases. Of these, Covid-Associated Pulmonary Aspergilliosis (CAPA) is a major concern with evidence that it occurs in the absence of traditional risk factors such as neutropenia and is diagnostically challenging for the attending physician. In this review, we focus on the immunopathology of SARS-CoV-2 and how this potentiates CAPA through dysregulation of local and systemic immunity as well as the unintended consequences of approved COVID treatments including corticosteroids and IL-6 inhibitors. Finally, we will consider how knowledge of the above may aid in the diagnosis of CAPA using current diagnostics and what treatment should be instituted in probable and confirmed cases.


Subject(s)
COVID-19/complications , COVID-19/immunology , Disease Susceptibility/immunology , Host-Pathogen Interactions/immunology , Pulmonary Aspergillosis/etiology , SARS-CoV-2/immunology , Antifungal Agents/therapeutic use , Biomarkers , COVID-19/virology , Disease Management , Humans , Immunocompromised Host , Pulmonary Aspergillosis/diagnosis , Pulmonary Aspergillosis/therapy , Reproducibility of Results , Serologic Tests/methods , Serologic Tests/standards , Treatment Outcome
5.
Molecules ; 27(4)2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35209238

ABSTRACT

For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, n = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (n = 24 total) were probed on AIT's 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of n = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of p < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed n = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/etiology , Autoantibodies/immunology , Autoimmunity , Biomarkers , Animals , Autoantibodies/blood , Autoantigens/immunology , Computational Biology/methods , Disease Models, Animal , Disease Susceptibility/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Protein Array Analysis , Rats , Severity of Illness Index
6.
Mol Med ; 28(1): 18, 2022 02 05.
Article in English | MEDLINE | ID: mdl-35123388

ABSTRACT

BACKGROUND: Although type 1 diabetes (T1D) is typically described as a T cell-mediated autoimmune disease, increasing evidence for a role of B cells has emerged. However, the pivotal disease-relevant B cell subset and its contribution to islet autoimmunity remain elusive. METHODS: The frequencies and phenotypic characteristics of circulating B cell subsets were analyzed using flow cytometry in individuals with new-onset T1D, long-term T1D, type 2 diabetes, and nondiabetic controls, and also in a prospective cohort of patients receiving mesenchymal stromal cell (MSC) transplantation. NOD mice and adoptive transfer assay were used to dissect the role of the certain B cell subset in disease progression. An in-vitro coculture system of islets with immune cells was established to examine the response against islets and the underlying mechanisms. RESULTS: We identified that plasmablasts, a B cell subset at the antibody-secreting stage, were significantly increased and correlated with the deterioration of beta cell function in patients with new-onset T1D. Further, a fall of plasmablast number was associated with the preservation of beta cell function in patients who received MSC transplantation after 3 months of follow-up. Meanwhile, a gradual increase of plasmablasts in pancreatic lymph nodes during the natural progression of insulitis was observed in non-obese diabetic (NOD) mice; adoptive transfer of plasmablasts together with T cells from NOD mice accelerated diabetes onset in NOD/SCID recipients. CONCLUSIONS: Our study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4+ T cells, further contributing to the T cell-mediated beta cell destruction. Our results provide insights into the pathogenic role of plasmablasts in islet autoimmunity and may offer new translational strategies for inhibiting T1D development.


Subject(s)
Diabetes Mellitus, Type 1/etiology , Diabetes Mellitus, Type 1/metabolism , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Biomarkers , Case-Control Studies , Diabetes Mellitus, Type 1/diagnosis , Disease Models, Animal , Disease Susceptibility/immunology , Female , Humans , Immunohistochemistry , Immunophenotyping , Insulin-Secreting Cells/pathology , Lymphocyte Activation , Male , Mice, SCID
7.
J Immunol ; 208(4): 785-792, 2022 02 15.
Article in English | MEDLINE | ID: mdl-35115374

ABSTRACT

Unlike the adaptive immune system, the innate immune system has classically been characterized as being devoid of memory functions. However, recent research shows that innate myeloid and lymphoid cells have the ability to retain memory of prior pathogen exposure and become primed to elicit a robust, broad-spectrum response to subsequent infection. This phenomenon has been termed innate immune memory or trained immunity. Innate immune memory is induced via activation of pattern recognition receptors and the actions of cytokines on hematopoietic progenitors and stem cells in bone marrow and innate leukocytes in the periphery. The trained phenotype is induced and sustained via epigenetic modifications that reprogram transcriptional patterns and metabolism. These modifications augment antimicrobial functions, such as leukocyte expansion, chemotaxis, phagocytosis, and microbial killing, to facilitate an augmented host response to infection. Alternatively, innate immune memory may contribute to the pathogenesis of chronic diseases, such as atherosclerosis and Alzheimer's disease.


Subject(s)
Communicable Diseases/etiology , Disease Susceptibility , Host-Pathogen Interactions/immunology , Immunity, Innate , Immunologic Memory , Animals , Biomarkers , Communicable Diseases/metabolism , Disease Resistance/genetics , Disease Resistance/immunology , Disease Susceptibility/immunology , Energy Metabolism , Epigenesis, Genetic , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Immune System/cytology , Immune System/immunology , Immune System/metabolism , Organ Specificity/genetics , Organ Specificity/immunology , Receptors, Pattern Recognition/metabolism , Signal Transduction
8.
Int J Mol Sci ; 23(2)2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35055087

ABSTRACT

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.


Subject(s)
Arthritis, Rheumatoid/etiology , Arthritis, Rheumatoid/metabolism , Disease Susceptibility/immunology , Animals , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/therapy , Biomarkers , Clinical Studies as Topic , Combined Modality Therapy , Disease Management , Disease Models, Animal , Humans , Immune System/cytology , Immune System/immunology , Immune System/metabolism , Molecular Diagnostic Techniques , Prognosis , Treatment Outcome
9.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: mdl-35074921

ABSTRACT

Proinflammatory cytokine production by innate immune cells plays a crucial role in inflammatory diseases, but the molecular mechanisms controlling the inflammatory responses are poorly understood. Here, we show that TANK-binding kinase 1 (TBK1) serves as a vital regulator of proinflammatory macrophage function and protects against tissue inflammation. Myeloid cell-conditional Tbk1 knockout (MKO) mice spontaneously developed adipose hypertrophy and metabolic disorders at old ages, associated with increased adipose tissue M1 macrophage infiltration and proinflammatory cytokine expression. When fed with a high-fat diet, the Tbk1-MKO mice also displayed exacerbated hepatic inflammation and insulin resistance, developing symptoms of nonalcoholic steatohepatitis. Furthermore, myeloid cell-specific TBK1 ablation exacerbates inflammation in experimental colitis. Mechanistically, TBK1 functions in macrophages to suppress the NF-κB and MAP kinase signaling pathways and thus attenuate induction of proinflammatory cytokines, particularly IL-1ß. Ablation of IL-1 receptor 1 (IL-1R1) eliminates the inflammatory symptoms of Tbk1-MKO mice. These results establish TBK1 as a pivotal anti-inflammatory mediator that restricts inflammation in different disease models.


Subject(s)
Inflammation/etiology , Inflammation/metabolism , Myeloid Cells/immunology , Myeloid Cells/metabolism , Protein Serine-Threonine Kinases/genetics , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Biomarkers , Colitis/etiology , Colitis/metabolism , Colitis/pathology , Cytokines/genetics , Cytokines/metabolism , Diet, High-Fat , Disease Models, Animal , Disease Susceptibility/immunology , Gene Expression Regulation , Glucose/metabolism , Hypertrophy , Immunomodulation/genetics , Inflammation/pathology , Inflammation Mediators/metabolism , Insulin Resistance , Mice , Mice, Knockout , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Organ Specificity , Protein Serine-Threonine Kinases/metabolism , Receptors, Interleukin-1/deficiency , Signal Transduction
10.
Int J Mol Sci ; 23(1)2022 Jan 04.
Article in English | MEDLINE | ID: mdl-35008950

ABSTRACT

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Host-Pathogen Interactions/immunology , Membrane Proteins/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Tuberculosis/microbiology , Antigens, Bacterial/chemistry , Antigens, Bacterial/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Disease Susceptibility/immunology , Glycine/metabolism , Humans , Immune Evasion , Immunomodulation , Macrophages/immunology , Macrophages/metabolism , Macrophages/microbiology , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Mycobacterium tuberculosis/metabolism , Virulence
11.
Mol Cancer ; 21(1): 15, 2022 01 14.
Article in English | MEDLINE | ID: mdl-35031075

ABSTRACT

Tumor-derived exosomes (TDEs) play pivotal roles in several aspects of cancer biology. It is now evident that TDEs also favor tumor growth by negatively affecting anti-tumor immunity. As important sentinels of immune surveillance system, natural killer (NK) cells can recognize malignant cells very early and counteract the tumor development and metastasis without a need for additional activation. Based on this rationale, adoptive transfer of ex vivo expanded NK cells/NK cell lines, such as NK-92 cells, has attracted great attention and is widely studied as a promising immunotherapy for cancer treatment. However, by exploiting various strategies, including secretion of exosomes, cancer cells are able to subvert NK cell responses. This paper reviews the roles of TDEs in cancer-induced NK cells impairments with mechanistic insights. The clinical significance and potential approaches to nullify the effects of TDEs on NK cells in cancer immunotherapy are also discussed.


Subject(s)
Exosomes/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Neoplasms/etiology , Neoplasms/metabolism , Animals , Biological Transport , Biomarkers , Cell Communication , Cell Survival , Cytokines/metabolism , Cytotoxicity, Immunologic , Disease Management , Disease Susceptibility/immunology , Energy Metabolism , Gene Expression Regulation , Humans , Immunotherapy , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Neoplasms/pathology , Neoplasms/therapy , Protein Binding , Signal Transduction
12.
Neoplasia ; 24(2): 145-154, 2022 02.
Article in English | MEDLINE | ID: mdl-34991061

ABSTRACT

A comprehensive evaluation of the clear cell renal cell carcinoma (ccRCC) immune landscape was found using 584 RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), we identified 17 key dysregulated immune-associated genes in ccRCC based on association with clinical variables and important immune pathways. Of the numerous findings from our analyses, we found that several of the 17 key dysregulated genes are heavily involved in interleukin and NF-kB signaling and that somatic copy number alteration (SCNA) hotspots may be causally associated with gene dysregulation. More importantly, we also found that key immune-associated genes and pathways are strongly upregulated in ccRCC. Our study may lend novel insights into the clinical implications of immune dysregulation in ccRCC and suggests potential immunotherapeutic targets for further evaluation.


Subject(s)
Carcinoma, Renal Cell/etiology , Disease Susceptibility/immunology , Kidney Neoplasms/etiology , Biomarkers , Carcinoma, Renal Cell/pathology , Gene Expression Regulation, Neoplastic , Humans , Immunity/genetics , Kidney Neoplasms/pathology , Signal Transduction
13.
PLoS Pathog ; 18(1): e1009948, 2022 01.
Article in English | MEDLINE | ID: mdl-34982799

ABSTRACT

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n = 30) or condom-protected (n = 8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners' cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.


Subject(s)
Coitus , Condoms , Disease Susceptibility/immunology , HIV Infections/immunology , Penis/immunology , Adult , Female , Humans , Male , Unsafe Sex , Vagina/immunology
14.
Int J Mol Sci ; 23(2)2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35054960

ABSTRACT

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.


Subject(s)
Biomarkers , Disease Susceptibility , Fatty Liver, Alcoholic/etiology , Fatty Liver, Alcoholic/metabolism , Hepatitis/complications , Hepatitis/metabolism , Oxidative Stress , Signal Transduction , Animals , Disease Susceptibility/immunology , Ethanol/adverse effects , Ethanol/metabolism , Fatty Liver/complications , Fatty Liver/etiology , Fatty Liver/metabolism , Fatty Liver, Alcoholic/pathology , Gene Expression Regulation , Hepatitis/etiology , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Immunity, Innate , Metabolic Networks and Pathways , MicroRNAs/genetics , Oxidation-Reduction
15.
Int J Mol Sci ; 23(2)2022 Jan 12.
Article in English | MEDLINE | ID: mdl-35054989

ABSTRACT

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1ß and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.


Subject(s)
Cardiovascular Diseases/etiology , Cardiovascular Diseases/therapy , Disease Susceptibility , Immunomodulation , Immunotherapy , Inflammation/complications , Animals , Biomarkers , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/metabolism , Disease Management , Disease Susceptibility/immunology , Feedback, Physiological , Gastrointestinal Microbiome/immunology , Humans , Immunomodulation/drug effects , Immunotherapy/adverse effects , Immunotherapy/methods , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Kidney Diseases/complications , Kidney Diseases/etiology , Molecular Targeted Therapy , Risk Factors , Treatment Outcome
16.
Int J Mol Sci ; 23(2)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35055001

ABSTRACT

Non-coding RNAs, particularly lncRNAs and miRNAs, have recently been shown to regulate different steps in viral infections and induction of immune responses against viruses. Expressions of several host and viral lncRNAs have been found to be altered during viral infection. These lncRNAs can exert antiviral function via inhibition of viral infection or stimulation of antiviral immune response. Some other lncRNAs can promote viral replication or suppress antiviral responses. The current review summarizes the interaction between ncRNAs and herpes simplex virus, cytomegalovirus, and Epstein-Barr infections. The data presented in this review helps identify viral-related regulators and proposes novel strategies for the prevention and treatment of viral infection.


Subject(s)
Disease Susceptibility , Host-Pathogen Interactions/genetics , RNA, Untranslated , Virus Diseases/etiology , Virus Replication , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , DNA Viruses/physiology , Disease Models, Animal , Disease Susceptibility/immunology , Gene Expression Regulation/drug effects , Gene Expression Regulation, Viral/drug effects , Host-Pathogen Interactions/immunology , Humans , Molecular Diagnostic Techniques , Protein Binding , Species Specificity , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Virus Diseases/metabolism , Virus Replication/drug effects
17.
Int J Mol Sci ; 23(2)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35055041

ABSTRACT

Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.


Subject(s)
Host-Pathogen Interactions , Neonatal Sepsis/microbiology , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/physiology , Age Factors , Bacterial Toxins/genetics , Biofilms , Disease Susceptibility/immunology , Host-Pathogen Interactions/immunology , Humans , Immune Tolerance , Immunity, Innate , Infant, Newborn , Neonatal Sepsis/diagnosis , Neonatal Sepsis/prevention & control , Neonatal Sepsis/therapy , Risk Factors , Staphylococcal Infections/diagnosis , Staphylococcal Infections/prevention & control , Staphylococcal Infections/therapy , Virulence/genetics , Virulence/immunology , Virulence Factors/genetics , Virulence Factors/immunology
18.
Mol Med ; 28(1): 10, 2022 01 29.
Article in English | MEDLINE | ID: mdl-35093033

ABSTRACT

BACKGROUND: Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host. MAIN BODY OF THE MANUSCRIPT: It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode. CONCLUSION: Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.


Subject(s)
Biofilms , Disease Susceptibility/immunology , Disease Susceptibility/metabolism , Host-Pathogen Interactions , Infections/etiology , Infections/metabolism , Neoplasms/complications , Animals , Biofilms/growth & development , Biomarkers , Disease Management , Energy Metabolism , Humans , Immune System/immunology , Immune System/metabolism , Infections/diagnosis , Infections/therapy , Neoplasms/etiology , Neoplasms/metabolism , Neoplasms/therapy , Organ Specificity
19.
Br J Haematol ; 196(2): 288-303, 2022 01.
Article in English | MEDLINE | ID: mdl-34355382

ABSTRACT

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by complement-mediated intravascular haemolysis, severe thrombophilia and bone marrow failure. While for patients with bone marrow failure the treatment follows that of immune-mediated aplastic anaemia, that of classic, haemolytic PNH is based on anti-complement medication. The anti-C5 monoclonal antibody eculizumab has revolutionized treatment, resulting in control of intravascular haemolysis and thromboembolic risk, with improved long-term survival. Novel strategies of complement inhibition are emerging. New anti-C5 agents reproduce the safety and efficacy of eculizumab, with improved patient convenience. Proximal complement inhibitors have been developed to address C3-mediated extra-vascular haemolysis and seem to improve haematological response.


Subject(s)
Hemoglobinuria, Paroxysmal/therapy , Algorithms , Clinical Decision-Making , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Disease Management , Disease Susceptibility/immunology , Genetic Predisposition to Disease , Hemoglobinuria, Paroxysmal/diagnosis , Hemoglobinuria, Paroxysmal/etiology , Humans , Phenotype , Prognosis , Standard of Care , Treatment Outcome
20.
Life Sci Alliance ; 5(3)2022 03.
Article in English | MEDLINE | ID: mdl-34853163

ABSTRACT

Acute-on-chronic liver failure (ACLF) is clinical syndrome with high mortality rate. This study aimed to perform detailed transcriptomic analysis in liver cirrhosis-based ACLF rats to elucidate ACLF pathogenesis. ACLF was induced by combined porcine serum with D-galactosamine and lipopolysaccharide. Gene expression profile of liver tissues from ACLF rats was generated by transcriptome sequencing to reveal the molecular mechanism. ACLF rats successfully developed with typical characteristics. Total of 2,354/3,576 differentially expressed genes were identified when ACLF was compared to liver cirrhosis and normal control, separately. The functional synergy analysis revealed prominent immune dysregulation at ACLF stage, whereas metabolic disruption was significantly down-regulated. Relative proportions of innate immune-related cells showed significant elevation of monocytes and macrophages, whereas adaptive immune-related cells were reduced. The seven differentially expressed genes underlying the ACLF molecular mechanisms were externally validated, among them THBS1, IL-10, and NR4A3 expressions were confirmed in rats, patient transcriptomics, and liver biopsies, verifying their potential value in the ACLF pathogenesis. This study indicates immune-metabolism disorder in ACLF rats, which may provide clinicians new targets for improving intervention strategies.


Subject(s)
Acute-On-Chronic Liver Failure/etiology , Acute-On-Chronic Liver Failure/metabolism , Disease Susceptibility , Energy Metabolism , Immunity , Acute-On-Chronic Liver Failure/pathology , Animals , Biomarkers , Cellular Microenvironment/genetics , Cellular Microenvironment/immunology , Disease Models, Animal , Disease Susceptibility/immunology , Gene Expression Profiling , Gene Expression Regulation , Liver/immunology , Liver/metabolism , Liver/pathology , Rats , Transcriptome
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