Repositorio Institucional Académico. Universidad Andrés Bello. Chile :: Examinando por Autor "Riedel, Claudia A."

Examinando por Autor "Riedel, Claudia A."

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Assessing the importance of domestic vaccine manufacturing centers: An overview of immunization programs, vaccine manufacture, and distribution
(Frontiers Media S.A., 2018-01) Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.
Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. © 2018 Rey-Jurado, Tapia, Muñoz-Durango, Lay, Carreño, Riedel, Bueno, Genzel and Kalergis.
Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease
(Communications Biology, Volume 7, Issue 1 December 2024, Article number 81, 2024-12) Duarte, Luisa F.; Villalobos, Verónica; Farías, Mónica A.; Rangel-Ramírez, Ma. Andreina; González-Madrid, Enrique; Navarro, Areli J.; Carbone-Schellman, Javier; Domínguez, Angélica; Alvarez, Alejandra; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS. © The Author(s) 2024.
Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis
(Frontiers Media S.A., 2021-02) Duarte, Luisa F.; Altamirano Lagos, María J.; Tabares Guevara, Jorge H.; Opazo, Ma. Cecilia; Díaz, Máximo; Navarrete, Romina; Muza, Catalina; Vallejos, Omar P.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.
Multiple sclerosis (MS) is an increasingly prevalent progressive autoimmune and debilitating chronic disease that involves the detrimental recognition of central nervous system (CNS) antigens by the immune system. Although significant progress has been made in the last decades on the biology of MS and the identification of novel therapies to treat its symptoms, the etiology of this disease remains unknown. However, recent studies have suggested that viral infections may contribute to disease onset. Interestingly, a potential association between herpes simplex virus type 1 (HSV-1) infection and MS has been reported, yet a direct relationship among both has not been conclusively demonstrated. Experimental autoimmune encephalomyelitis (EAE) recapitulates several aspects of MS in humans and is widely used to study this disease. Here, we evaluated the effect of asymptomatic brain infection by HSV-1 on the onset and severity of EAE in C57BL/6 mice. We also evaluated the effect of infection with an HSV-1-mutant that is attenuated in neurovirulence and does not cause encephalitis. Importantly, we observed more severe EAE in mice previously infected either, with the wild-type (WT) or the mutant HSV-1, as compared to uninfected control mice. Also, earlier EAE onset was seen after WT virus inoculation. These findings support the notion that a previous exposure to HSV-1 can accelerate and enhance EAE, which suggests a potential contribution of asymptomatic HSV-1 to the onset and severity of MS. © Copyright © 2021 Duarte, Altamirano-Lagos, Tabares-Guevara, Opazo, Díaz, Navarrete, Muza, Vallejos, Riedel, Bueno, Kalergis and González.
Characterization of the Anti-Inflammatory Capacity of IL-10-Producing Neutrophils in Response to Streptococcus pneumoniae Infection
(Frontiers Media S.A., 2021-04) González, Liliana A.; Melo González, Felipe; Sebastián, Valentina P.; Vallejos, Omar P.; Noguera, Loreani P.; Suazo, Isidora D.; Schultz, Bárbara M.; Manosalva, Andrés H.; Peñaloza, Hernán F.; Soto, Jorge A.; Parker, Dane; Riedel, Claudia A.; González, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.
Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/-) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival. © Copyright © 2021 González, Melo-González, Sebastián, Vallejos, Noguera, Suazo, Schultz, Manosalva, Peñaloza, Soto, Parker, Riedel, González, Kalergis and Bueno.
Conjugal transfer of the pathogenicity island ROD21 in salmonella enterica serovar enteritidis depends on environmental conditions
(Public Library of Science, 2014-04) Salazar-Echegarai, Francisco J.; Tobar, Hugo E.; Nieto, Pamela A.; Riedel, Claudia A.; Bueno, Susan M.
Unstable pathogenicity islands are chromosomal elements that can be transferred from one bacterium to another. Salmonella enterica serovar Enteritidis (S. Enteritidis) is a pathogenic bacterium containing such unstable pathogenicity islands. One of them, denominated ROD21, is 26.5 kb in size and capable of excising from the chromosome in certain culture conditions, as well as during bacterial infection of phagocytic cells. In this study we have evaluated whether ROD21 can be effectively transferred from one bacterium to another. We generated a donor and several recipient strains of S. Enteritidis to carry out transfer assays in liquid LB medium. These assays showed that ROD21 is effectively transferred from donor to recipient strains of S. Enteritidis and S. Typhimurium. When Escherichia coli was used as the recipient strain, ROD21 transfer failed to be observed. Subsequently, we showed that a conjugative process was required for the transfer of the island and that changes in temperature and pH increased the transfer frequency between Salmonella strains. Our data indicate that ROD21 is an unstable pathogenicity island that can be transferred by conjugation in a species-specific manner between Salmonellae. Further, ROD21 transfer frequency increases in response to environmental changes, such as pH and temperature.
Contribution of autophagy to antiviral immunity
(Elsevier B.V., 2015-05) Rey-Jurado, Emma; Riedel, Claudia A.; González, Pablo A.; Bueno, Susan M.; Kalergis, Alexis M.
Although identified in the 1960's, interest in autophagy has significantly increased in the past decade with notable research efforts oriented at understanding as to how this multi-protein complex operates and is regulated. Autophagy is commonly defined as a "self-eating" process evolved by eukaryotic cells to recycle senescent organelles and expired proteins, which is significantly increased during cellular stress responses. In addition, autophagy can also play important roles during human diseases, such as cancer, neurodegenerative and autoimmune disorders. Furthermore, novel findings suggest that autophagy contributes to the host defense against microbial infections. In this article, we review the role of macroautophagy in antiviral immune responses and discuss molecular mechanisms evolved by viral pathogens to evade this process. A role for autophagy as an effector mechanism used both, by innate and adaptive immunity is also discussed. © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Contribution of dendritic cells to the autoimmune pathology of systemic lupus erythematosus
(Blackwell Publishing Ltd, 2015-12) Mackern-Oberti, Juan P.; Llanos, Carolina; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
Systemic lupus erythematosus (SLE) is a heterogeneous disease in which excessive inflammation, autoantibodies and complement activation lead to multisystem tissue damage. The contribution of the individual genetic composition has been extensively studied, and several susceptibility genes related to immune pathways that participate in SLE pathogenesis have been identified. It has been proposed that SLE takes place when suscepti bility factors interact with environmental stimuli leading to a deregulated immune response. Experimental evidence suggests that such events are related to the failure of T-cell and B-cell suppression mediated by defects in cell signalling, immune tolerance and apoptotic mechanism promoting autoimmunity. In addition, it has been reported that dendritic cells (DCs) from SLE patients, which are crucial in the modulation of peripheral tol erance to self-antigens, show an increased ratio of activating/inhibitory receptors on their surfaces. This phenotype and an augmented expression of co-stimulatory molecules is thought to be critical for disease pathogen esis. Accordingly, tolerogenic DCs can be a potential strategy for develop ing antigen-specific therapies to reduce detrimental inflammation without causing systemic immunosuppression. In this review article we discuss the most relevant data relative to the contribution of DCs to the triggering of SLE.
Contribution of viral and bacterial infections to senescence and immunosenescence
(Frontiers Media SA, 2023) Reyes, Antonia; Ortiz, Gerardo; Duarte, Luisa F.; Fernández, Christian; Hernández-Armengol, Rosario; Palacios, Pablo A.; Prado, Yolanda; Andrade, Catalina A.; Rodriguez-Guilarte, Linmar; Kalergis, Alexis M.; Simon, Felipe; Carreño, Leandro J.; Riedel, Claudia A.; Cáceres, Mónica; González, Pablo A.
Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host’s susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review. Copyright © 2023 Reyes, Ortiz, Duarte, Fernández, Hernández-Armengol, Palacios, Prado, Andrade, Rodriguez-Guilarte, Kalergis, Simon, Carreño, Riedel, Cáceres and González.
Copper deficiency-induced anemia is caused by a mitochondrial metabolic reprograming in erythropoietic cells
(Metallomics, 2019-02) Jensen, Erik L.; Gonzalez-Ibanez, Alvaro M.; Mendoza, Pierina; Ruiz, Lina M.; Riedel, Claudia A.; Simon, Felipe; Schuringa, Jan J.; Elorza, Alvaro A.
The lack of copper has been associated with anemia, myelodysplastic syndromes and leukemia as well as with a loss in complex IV activity and an enlarged mitochondrial morphology. Mitochondria play a key role during the differentiation of hematopoietic stem cells by regulating the passage from a glycolytic to oxidative metabolism. The former is associated with cell proliferation and the latter with cell differentiation. Oxidative metabolism, which occurs inside mitochondria, is sustained by the respiratory chain, where complex IV is copper-dependent. We have hypothesized that a copper deficiency induces a mitochondrial metabolic reprogramming, favoring cell expansion over cell differentiation in erythropoiesis. Erythroid progression analysis of the bone marrow of mice fed with a copper deficient diet and of the in vitro erythropoiesis of human CD34+ cells treated with a bathocuproine-a copper chelator-showed a major expansion of progenitor cells and a decreased differentiation. Under copper deficiency, mitochondria switched to a higher membrane potential, lower oxygen consumption rate and lower ROS levels as compared with control cells. In addition, mitochondrial biomass was increased and an up-regulation of the mitochondrial fusion protein mitofusin 2 was observed. Most copper-deficient phenotypes were mimicked by the pharmacological inhibition of complex IV with azide. We concluded that copper deficiency induced a mitochondrial metabolic reprogramming, making hematopoietic stem cells favor progenitor cell expansion over cell differentiation.
Differential Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Response in Inactivated Virus-Vaccinated, Convalescent, and Breakthrough-Infected Subjects
(Oxford University Press, 2023-10-01) Duarte, Luisa F.; Vázquez, Yaneisi; Diethelm-Varela, Benjamín; Pavez, Valentina; Berríos-Rojas, Roslye; Méndez, Constanza; Riedel, Claudia A.; White, Jessica A.; Kalergis, Alexis M.; Bueno, Susan M.; González, Pablo A.
Background: We sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] inactivated vaccine), natural infection, or breakthrough infection. Methods: Serum samples obtained from volunteers immunized with CoronaVac (2 and 3 doses), breakthrough case patients, and from convalescent individuals were analyzed to determine the immunoglobulin (Ig) G responses against 3 structural and 8 nonstructural SARS-CoV-2 antigens. Results: Immunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared with convalescent subjects both after primary vaccination and after a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleocapsid (N) protein, similar to convalescent subjects. Breakthrough case patients produced the highest antibody levels against the N and M proteins. Antibodies against nonstructural viral proteins were present in >50% of the convalescent subjects. Conclusions: Vaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac. © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats
(MDPI, 2023-03) Prado, Yolanda; Echeverría, Cesar; Feijóo, Carmen G.; Riedel, Claudia A.; Cabello-Verrugio, Claudio; Santibanez, Juan F.; Simon, Felipe
Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment. © 2023 by the authors.
Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes
(Frontiers Media S.A., 2022-09) Funes, Samanta C.; Ríos, Mariana; Fernández Fierro, Ayleen; Rivera Pérez, Daniela; Soto, Jorge A.; Valbuena, José R.; Altamirano Lagos, María J; Gómez Santander, Felipe; Jara, Evelyn L.; Zoroquiain, Pablo; Roa, Juan C.; Kalergis, Alexis M.; Riedel, Claudia A.
Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71+ and FasL+) CD8+ T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV. Copyright © 2022 Funes, Ríos, Fernández-Fierro, Rivera-Pérez, Soto, Valbuena, Altamirano-Lagos, Gómez-Santander, Jara, Zoroquiain, Roa, Kalergis and Riedel.
Gestational hypothyroidism improves the ability of the female offspring to clear streptococcus pneumoniae infection and to recover from pneumococcal pneumonia
(Endocrine Society, 2016-06) Nieto, Pamela A.; Peñaloza, Hernán F.; Salazar-Echegarai, Francisco J.; Castellanos, Raquel M.; Opazo, Maria Cecilia; Venegas, Luis; Padilla, Oslando; Kalergis, Alexis M.; Riedel, Claudia A.; Bueno, Susan M.
Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections. In this study, we have evaluated whether adult mice gestated in hypothyroid mothers have an altered response to pneumococcal pneumonia. We observed that female mice gestated in hypothyroidism have increased survival rate and less bacterial dissemination to blood and brain after an intranasal challenge with Streptococcus pneumoniae. Further, these mice had higher amounts of inflammatory cells in the lungs and reduced production of cytokines characteristic of sepsis in spleen, blood, and brain at 48 hours after infection. Interestingly, mice gestated in hypothyroid mothers had basally increased vascular permeability in the lungs. These observations suggest that gestational hypothyroidism alters the immune response and the physiology of lungs in the offspring, increasing the resistance to respiratory bacterial infections.
Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes
(Frontiers Media SA, 2024-04) González-Madrid, Enrique; Rangel-Ramírez, Ma. Andreina; Opazo, María C.; Méndez, Luis; Bohmwald, Karen; Bueno, Susan M.; González, Pablo A.; Kalergis, Alexis M.; Riedel, Claudia A.
Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1β, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.
Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection
(MDPI, 2023-05) Tognarelli, Eduardo I.; Duarte, Luisa F.; Farías, Mónica A.; Cancino, Felipe A.; Corrales, Nicolás; Ibáñez, Francisco J.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1. © 2023 by the authors.
Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection
(American Association of Immunologists, 2017-07) Espinoza, Janyra A.; León, Miguel A.; Céspedes, Pablo F.; Gómez, Roberto S.; Canedo-Marroquín, Gisela; Riquelme, Sebastían A.; Salazar-Echegarai, Francisco J.; Blancou, Phillipe; Simon, Thomas; Anegon, Ignacio; Lay, Margarita K.; González, Pablo A.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection. Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.
Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity
(Frontiers Media SA, 2024) Sepúlveda-Alfaro, Javiera; Catalán, Eduardo A.; Vallejos, Omar P.; Ramos-Tapia, Ignacio; Madrid-Muñoz, Cristóbal; Mendoza-León, María J.; Suazo, Isidora D.; Rivera-Asin, Elizabeth; Silva, Pedro H.; Alvarez-Mardones, Oscar; Castillo-Godoy, Daniela P.; Riedel, Claudia A.; Schinnerling, Katina; Ugalde, Juan A.; Soto, Jorge A.; Bueno, Susan M.; Kalergis, Alexis M.; Melo-Gonzalez, Felipe
Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
Identification of biomarkers for disease severity in nasopharyngeal secretions of infants with upper or lower respiratory tract viral infections
(Oxford University Press, 2022-10) Bertrand, Pablo J.; Vázquez, Yaneisi; Beckhaus, Andrea A.; González, Liliana A.; Contreras, Ana María; Ferres, Marcela; Padilla, Oslando; Riedel, Claudia A.; Kalergis, Alexis M.; Bueno, Susan M.
Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV. © 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved.
IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule
(Frontiers Media S.A., 2021-07) Tabares Guevara, Jorge H.; Jaramillo, Julio C.; Ospina Quintero, Laura; Piedrahíta Ochoa, Christian A.; García Valencia, Natalia; Bautista Erazo, David E.; Caro Gómez, Erika; Covián, Camila; Retamal Díaz, Angello; Duarte, Luisa F.; González, Pablo A.; Bueno, Susan M.; Riedel, Claudia A.; Kalergis, Alexis M.; Ramírez Pineda, José R.
One of the interventional strategies to reestablish the immune effector/regulatory balance, that is typically altered in chronic inflammatory diseases (CID), is the reinforcement of endogenous immunomodulatory pathways as the one triggered by interleukin (IL)-10. In a recent work, we demonstrated that the subcutaneous (sc) administration of an IL-10/Treg-inducing small molecule-based formulation, using a repetitive microdose (REMID) treatment strategy to preferentially direct the effects to the regional immune system, delays the progression of atherosclerosis. Here we investigated whether the same approach using other IL-10-inducing small molecule, such as the safe, inexpensive, and widely available polyphenol curcumin, could induce a similar protective effect in two different CID models. We found that, in apolipoprotein E deficient mice, sc treatment with curcumin following the REMID strategy induced atheroprotection that was not consequence of its direct systemic lipid-modifying or antioxidant activity, but instead paralleled immunomodulatory effects, such as reduced proatherogenic IFNγ/TNFα-producing cells and increased atheroprotective FOXP3+ Tregs and IL-10-producing dendritic and B cells. Remarkably, when a similar strategy was used in the neuroinflammatory model of experimental autoimmune encephalomyelitis (EAE), significant clinical and histopathological protective effects were evidenced, and these were related to an improved effector/regulatory cytokine balance in restimulated splenocytes. The essential role of curcumin-induced IL-10 for neuroprotection was confirmed by the complete abrogation of the clinical effects in IL-10-deficient mice. Finally, the translational therapeutic prospection of this strategy was evidenced by the neuroprotection observed in mice starting the treatment one week after disease triggering. Collectively, results demonstrate the power of a simple natural IL-10-inducing small molecule to tackle chronic inflammation, when its classical systemic and direct pharmacological view is shifted towards the targeting of regional immune cells, in order to rationally harness its immunopharmacological potential. This shift implies that many well-known IL-10-inducing small molecules could be easily reformulated and repurposed to develop safe, innovative, and accessible immune-based interventions for CID. © Copyright © 2021 Tabares-Guevara, Jaramillo, Ospina-Quintero, Piedrahíta-Ochoa, García-Valencia, Bautista-Erazo, Caro-Gómez, Covián, Retamal-Díaz, Duarte, González, Bueno, Riedel, Kalergis and Ramírez-Pineda.
Is there a role for herpes simplex virus type 1 in multiple sclerosis?
(Elsevier Masson s.r.l., 2023-06) Duarte, Luisa F.; Gatica, Sebastian; Castillo, Almendra; Kalergis, Alexis M.; Bueno, Susan M.; Riedel, Claudia A.; González, Pablo A.
Numerous studies relate the onset and severity of multiple sclerosis (MS) with viral infections. Herpes simplex virus type 1 (HSV-1), which is neurotropic and highly prevalent in the brain of healthy in dividuals, has been proposed to relate to MS. Here, we review and discuss the reported connections between HSV-1 and MS. © 2022 The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Examinando por Autor "Riedel, Claudia A."

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