RESUMEN
NT1 is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the hypocretin (HCRT)/orexin neuropeptides in the lateral hypothalamus. While the exact etiology of NT1 is still unknown, numerous studies have provided compelling evidence supporting its autoimmune origin. The prevailing hypothetical view on the pathogenesis of NT1 involves an immune-mediated loss of HCRT neurons that can be triggered by Pandemrix® vaccination and/or by infection in genetically susceptible patients, specifically carriers of the HLA-DQB1*06:02 MHC class II allele. The molecular mechanisms by which infection/vaccination can induce autoimmunity in the case of NT1 remain to be elucidated. In this review, evidence regarding the involvement of vaccination and infection and the potential mechanisms by which it could be linked to the pathogenesis of NT1 will be discussed in light of the existing findings in other autoimmune diseases.
Asunto(s)
Narcolepsia , Vacunación , Humanos , Narcolepsia/inmunología , Narcolepsia/inducido químicamente , Narcolepsia/etiología , Vacunación/efectos adversos , Animales , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Orexinas/metabolismo , Cadenas beta de HLA-DQ/genética , Infecciones/inmunologíaAsunto(s)
Anticuerpos Neutralizantes , Autoanticuerpos , Síndromes de Inmunodeficiencia , Infecciones , Interleucina-23 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/inmunología , Interleucina-23/inmunología , Infecciones/sangre , Infecciones/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunologíaRESUMEN
Glycans play critical roles in the host-pathogen interactions leading to infection. However, we still understand very little about the dynamic nature of glycosylation in response to infection and its function in modulating host immunity. Many of the host proteins involved in immune defense are glycoproteins. Furthermore, the innate immune system recognizes glycans. The glycoform of a protein can impact proteolytic stability, receptor interactions, serum half-life, and other aspects. New, cutting-edge chemical biology tools are shedding light on the interplay between infection and the host glycome. In this review, we highlight new work on the importance of dynamic glycosylation of host proteins in the innate and adaptive immune pathways in response to infection. These include recent findings on altered glycoprofiles of mucins, complement components, and antibodies.
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Interacciones Huésped-Patógeno , Inmunidad Innata , Polisacáridos , Humanos , Glicosilación , Polisacáridos/metabolismo , Polisacáridos/química , Animales , Glicoproteínas/metabolismo , Inmunidad Adaptativa , Infecciones/inmunologíaRESUMEN
Regulated cell death (RCD) pathways, such as pyroptosis, apoptosis, and necroptosis, are essential for maintaining the body's balance, defending against pathogens, and eliminating abnormal cells that could lead to diseases like cancer. Although these pathways operate through distinct mechanisms, recent genetic and pharmacological studies have shown that they can interact and influence each other. The concept of "PANoptosis" has emerged, highlighting the interplay between pyroptosis, apoptosis, and necroptosis, especially during cellular responses to infections. This article provides a concise overview of PANoptosis and its molecular mechanisms, exploring its implications in various diseases. The review focuses on the extensive interactions among different RCD pathways, emphasizing the role of PANoptosis in infections, cytokine storms, inflammatory diseases, and cancer. Understanding PANoptosis is crucial for developing novel treatments for conditions involving infections, sterile inflammations, and cancer.
Asunto(s)
Inflamación , Necroptosis , Neoplasias , Piroptosis , Humanos , Inflamación/patología , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Animales , Necroptosis/efectos de los fármacos , Necroptosis/fisiología , Piroptosis/efectos de los fármacos , Piroptosis/fisiología , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Muerte Celular/fisiología , Muerte Celular Regulada/efectos de los fármacos , Infecciones/patología , Infecciones/inmunologíaRESUMEN
The neonatal Fc receptor (FcRn) can transport IgG and antigen-antibody complexes participating in mucosal immune responses that protect the host from most pathogens' invasion via the respiratory, digestive, and urogenital tracts. FcRn expression can be triggered upon stimulation with pathogenic invasion on mucosal surfaces, which may significantly modulate the innate immune response of the host. As an immunoglobulin transport receptor, FcRn is implicated in the pathophysiology of immune-related diseases such as infection and autoimmune disorders. In this review, we thoroughly summarize the recent advancement of FcRn in mucosal immunity and its therapeutic strategy. This includes insights into its regulation mechanisms of FcRn expression influenced by pathogens, its emerging role in mucosal immunity and its potential probability as a therapeutic target in infection and autoimmune diseases.
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Antígenos de Histocompatibilidad Clase I , Inmunidad Mucosa , Receptores Fc , Humanos , Receptores Fc/inmunología , Receptores Fc/metabolismo , Animales , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Infecciones/inmunología , Inmunidad InnataRESUMEN
Macrophages (MACs) and classical dendritic cells (cDCs) represent the front line of immune defense, playing crucial roles in both innate and adaptive immunity due to their remarkable tissue specificity and precise adaptation to environmental cues. MACs contribute to maintaining tissue homeostasis and immune surveillance, while cDCs function as the most efficient antigen-presenting cells, playing a critical role in immune responses. These two cell types share similarities and interconnections. Both MACs and cDCs are capable of recognizing pathogens and tissue damage, secreting cytokines to activate other innate immune cells, and initiating or modulating adaptive immunity through interactions with T cells. In this review, we provide a comprehensive analysis of the research advances in the development and functions of MACs and cDCs during resting and infection processes, elucidate their interrelationships and interactions within the immune system, and offer a theoretical basis for in-depth studies of diseases.
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Células Dendríticas , Macrófagos , Células Dendríticas/inmunología , Humanos , Macrófagos/inmunología , Animales , Infecciones/inmunología , Inmunidad Innata , Inmunidad AdaptativaRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.
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Deficiencia de Glucosafosfato Deshidrogenasa , Glucosafosfato Deshidrogenasa , Humanos , Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/inmunología , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Animales , Especies Reactivas de Oxígeno/metabolismo , Vía de Pentosa Fosfato , Inmunidad , Infecciones/inmunología , Inflamación/inmunología , Inflamación/metabolismoRESUMEN
Reactive oxygen species (ROS) contain at least one oxygen atom and one or more unpaired electrons and include singlet oxygen, superoxide anion radical, hydroxyl radical, hydroperoxyl radical, and free nitrogen radicals. Intracellular ROS can be formed as a consequence of several factors, including ultra-violet (UV) radiation, electron leakage during aerobic respiration, inflammatory responses mediated by macrophages, and other external stimuli or stress. The enhanced production of ROS is termed oxidative stress and this leads to cellular damage, such as protein carbonylation, lipid peroxidation, deoxyribonucleic acid (DNA) damage, and base modifications. This damage may manifest in various pathological states, including ageing, cancer, neurological diseases, and metabolic disorders like diabetes. On the other hand, the optimum levels of ROS have been implicated in the regulation of many important physiological processes. For example, the ROS generated in the mitochondria (mitochondrial ROS or mt-ROS), as a byproduct of the electron transport chain (ETC), participate in a plethora of physiological functions, which include ageing, cell growth, cell proliferation, and immune response and regulation. In this current review, we will focus on the mechanisms by which mt-ROS regulate different pathways of host immune responses in the context of infection by bacteria, protozoan parasites, viruses, and fungi. We will also discuss how these pathogens, in turn, modulate mt-ROS to evade host immunity. We will conclude by briefly giving an overview of the potential therapeutic approaches involving mt-ROS in infectious diseases.
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Mitocondrias , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Humanos , Mitocondrias/metabolismo , Animales , Estrés Oxidativo , Infecciones/metabolismo , Infecciones/inmunología , InmunidadRESUMEN
Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.
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Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Factores de Tiempo , Inmunoglobulinas/sangre , Factores de Riesgo , Agammaglobulinemia/sangre , Agammaglobulinemia/inmunología , Agammaglobulinemia/etiología , Biomarcadores/sangre , Infecciones/etiología , Infecciones/inmunología , Infecciones/sangre , Infecciones/epidemiologíaRESUMEN
Microalgal emergence is a promising platform with two-decade historical background for producing vaccines and biopharmaceuticals. During that period, microalgal-based vaccines have reported successful production for various diseases. Thus, species selection is important for genetic transformation and delivery methods that have been developed. Although many vaccine prototypes have been produced for infectious and non-infectious diseases, fewer studies have reached immunological and immunoprotective evaluations. Microalgae-made vaccines for Staphylococcus aureus, malaria, influenza, human papilloma, and Zika viruses have been explored in their capacity to induce humoral or cellular immune responses and protective efficacies against experimental challenges. Therefore, specific pathogen antigens and immune system role are important and addressed in controlling these infections. Regarding non-communicable diseases, these vaccines have been investigated for breast cancer; microalgal-produced therapeutic molecules and microalgal-made interferon-α have been explored for hypertension and potential applications in treating viral infections and cancer, respectively. Thus, conducting immunological trials is emphasized, discussing the promising results observed in terms of immunogenicity, desired immune response for controlling affections, and challenges for achieving the desired protection levels. The potential advantages and hurdles associated with this innovative approach are highlighted, underlining the relevance of assessing immune responses in preclinical and clinical trials to validate the efficacy of these biopharmaceuticals. The promising future of this healthcare technology is also envisaged.
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Microalgas , Vacunas Sintéticas , Animales , Humanos , Microalgas/genética , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Infecciones/inmunología , Control de InfeccionesRESUMEN
Mammalian brain border-associated macrophages (BAMs) are strategically positioned to support vital properties and processes: for example, the composition of the brain's perivascular extracellular matrix and cerebrospinal fluid flow via the glymphatic pathway. BAMs also effectively restrict the spread of infectious microbes into the brain. However, while fighting infections, BAMs sustain long-term transcriptomic changes and can be replaced by inflammatory monocytes, potentially leading to a gradual loss of their beneficial homeostatic functions. We hypothesize that by expediting the deterioration of BAMs, multiple infection episodes might be associated with accelerated brain aging and the putative development of neurodegenerative diseases. Our viewpoint is supported by recent studies suggesting that rejuvenating aged BAMs, and counterbalancing their detrimental inflammatory signatures during infections, might hold promise in treating aging-related neurological disorders, including Alzheimer's disease (AD).
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Envejecimiento , Enfermedad de Alzheimer , Encéfalo , Macrófagos , Animales , Humanos , Envejecimiento/inmunología , Enfermedad de Alzheimer/inmunología , Encéfalo/inmunología , Encéfalo/patología , Infecciones/inmunología , Macrófagos/inmunologíaRESUMEN
OBJECTIVE: To investigate the association between serum immunoglobulin G (IgG) concentrations and the incidence of infections in patients with chronic lymphocytic leukemia (CLL) and secondary immunodeficiency receiving treatment with Privigen. MATERIALS AND METHODS: Data was analyzed from a non-interventional study conducted in 31 centers in Germany and 1 in Austria. Adult CLL patients with hypogammaglobulinemia and recurrent infections were allowed to enter the study upon signing informed consent, if a prior decision for treatment with Privigen had been made. All infections requiring an antimicrobial treatment were subject to analysis. Patients were stratified according to their mean post-baseline serum IgG trough levels in a group with lower IgG trough levels (≤ 5.0 g/L), and a group with higher IgG trough levels (> 5.0 g/L). RESULTS: Overall, 89 patients and 840 treatment cycles were analyzed. Up to 11 treatment cycles (average duration 29 days) were documented in each patient. In the group with higher IgG trough levels (> 5.0 g/L, N = 72), significantly fewer infections were observed than in the group with lower IgG trough levels (≤ 5.0 g/L, N = 17), including fewer severe and serious infections. The Privigen dosage was a major determinant of the post-baseline serum IgG levels. Overall tolerability of Privigen was assessed as very good or good in 91% of patients. CONCLUSION: This analysis confirms the association of serum IgG trough levels with the incidence of infections and highlights the importance of careful monitoring of IgG levels during treatment of secondary immunodeficiencies in CLL patients.
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Inmunoglobulina G , Leucemia Linfocítica Crónica de Células B , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agammaglobulinemia/epidemiología , Agammaglobulinemia/inmunología , Agammaglobulinemia/sangre , Alemania/epidemiología , Inmunoglobulina G/sangre , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/complicaciones , Incidencia , Infecciones/epidemiología , Infecciones/inmunología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/sangreRESUMEN
Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell-dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T-helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin-CD4+ T-cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T-cell activation, which is initially triggered by IL-12p40- and MHC-II-dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the thrombin-activatable fibrinolysis inhibitor (TAFI) with fibrin whereby fibrin deposition is increased by TAFI in the absence but not in the presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1-dependent T-helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.
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Linfocitos T CD4-Positivos , Fibrina , Humanos , Fibrina/metabolismo , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Infecciones/inmunología , Activación de Linfocitos/inmunología , Trombosis/etiología , Trombosis/inmunologíaRESUMEN
BACKGROUND: L-Tryptophan (L-Trp), an essential amino acid, is the only amino acid whose level is regulated specifically by immune signals. Most proportions of Trp are catabolized via the kynurenine (Kyn) pathway (KP) which has evolved to align the food availability and environmental stimulation with the host pathophysiology and behavior. Especially, the KP plays an indispensable role in balancing the immune activation and tolerance in response to pathogens. SCOPE OF REVIEW: In this review, we elucidate the underlying immunological regulatory network of Trp and its KP-dependent catabolites in the pathophysiological conditions by participating in multiple signaling pathways. Furthermore, the KP-based regulatory roles, biomarkers, and therapeutic strategies in pathologically immune disorders are summarized covering from acute to chronic infection and inflammation. MAJOR CONCLUSIONS: The immunosuppressive effects dominate the functions of KP induced-Trp depletion and KP-produced metabolites during infection and inflammation. However, the extending minor branches from the KP are not confined to the immune tolerance, instead they go forward to various functions according to the specific condition. Nevertheless, persistent efforts should be made before the clinical use of KP-based strategies to monitor and cure infectious and inflammatory diseases.
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Biomarcadores , Inflamación , Quinurenina , Triptófano , Triptófano/metabolismo , Quinurenina/metabolismo , Humanos , Inflamación/metabolismo , Inflamación/inmunología , Animales , Biomarcadores/metabolismo , Infecciones/inmunología , Infecciones/metabolismoRESUMEN
Multiple epidemiologic studies have revealed that gender is considered one of the important factors in the frequency and severity of certain infectious diseases, in which estrogens may play a vital role. There is growing evidence that estrogens as female sex hormone can modulate multiple biological functions outside of the reproductive system, such as in brain and cardiovascular system. However, it is largely unknown about the roles and mechanisms of estrogens/estrogen receptors in immune health and infection disease. Thence, by reading a lot of literature, we summarized the regulatory mechanisms of estrogens/estrogen receptors in immune cells and their roles in certain infectious diseases with gender differences. Therefore, estrogens may have therapeutic potentials to prevent and treat these infectious diseases, which needs further clinical investigation.
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Estrógenos , Humanos , Estrógenos/metabolismo , Estrógenos/inmunología , Animales , Receptores de Estrógenos/metabolismo , Sistema Inmunológico/metabolismo , Sistema Inmunológico/inmunología , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/metabolismo , Infecciones/inmunologíaAsunto(s)
Anticuerpos Biespecíficos , Linfoma , Humanos , Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Infecciones/etiología , Infecciones/tratamiento farmacológico , Infecciones/inmunología , Linfoma/tratamiento farmacológico , Linfoma/inmunología , Linfoma/terapiaRESUMEN
On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage. In addition, diverse areas of alcohol research covered multiple pathways behind alcohol-induced cellular dysfunction, including inflammasome activation, changes in miRNA expression, mitochondrial metabolism, gene regulation, and transcriptomics. Finally, the work presented at this meeting highlighted novel biomarkers and therapeutic interventions for patients suffering from alcohol-induced organ damage.