Examinando por Autor "Kalergis, A.M."
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Ítem Aberrant T cell immunity triggered by human respiratory syncytial virus and human metapneumovirus infection(Taylor and Francis, 2017-08) González, A.E.; Lay, M.K.; Jara, E.L.; Espinoza, J.A.; Gómez, R.S.; Soto, J.; Rivera, C.A.; Abarca, K.; Bueno, S.M.; Riedel, C.A.; Kalergis, A.M.Human Respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are the two major etiological viral agents of lower respiratory tract diseases, affecting mainly infants, young children and the elderly. Although the infection of both viruses trigger an antiviral immune response that mediate viral clearance and disease resolution in immunocompetent individuals, the promotion of long-term immunity appears to be deficient and reinfection are common throughout life. A possible explanation for this phenomenon is that hRSV and hMPV, can induce aberrant T cell responses, which leads to exacerbated lung inflammation and poor T and B cell memory immunity. The modulation of immune response exerted by both viruses include different strategies such as, impairment of immunological synapse mediated by viral proteins or soluble factors, and the induction of pro-inflammatory cytokines by epithelial cells, among others. All these viral strategies contribute to the alteration of the adaptive immunity in order to increase the susceptibility to reinfections. In this review, we discuss current research related to the mechanisms underlying the impairment of T and B cell immune responses induced by hRSV and hMPV infection. In addition, we described the role each virulence factor involved in immune modulation caused by these viruses. © 2017 Taylor & Francis.Ítem Assessing the importance of domestic vaccine manufacturing centers: An overview of immunization programs, vaccine manufacture, and distribution(Frontiers Media, 2018-01) Rey-Jurado, E.; Tapia, F.; Muñoz-Durango, N.; Lay, M.K.; Carreño, L.J.; Riedel, C.A.; Bueno, S.M.; Genzel, Y.; Kalergis, A.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.Ítem Eplerenone Implantation Improved Adipose Dysfunction Averting RAAS Activation and Cell Division(Frontiers Media S.A., 2020-04) Vecchiola, A.; Fuentes, C.A.; Solar, I.; Lagos, C.F.; Opazo, M.C.; Muñoz-Durango, N.; Riedel, C.A.; Owen, G.I.; Kalergis, A.M.; Fardella, C.E.Introduction: Mineralocorticoid receptor (MR) activation within adipose tissue, triggers inflammation and metabolic syndrome development. The pharmacological blockade of MR provides beneficial effects for adipose tissue. Our study evaluates the impact of eplerenone implantation upon obesity. Experimental approach: A group of mice with implanted placebo pellets were fed using two types of diet, a normal (ND) or a high fat (HFD) diet. Additionally, a group of mice fed HFD were implanted with an eplerenone pellet. Metabolic and biochemical parameters were assessed in each animal group. Adipocyte size and lipid accumulation were investigated in the liver and adipose tissue. We evaluated the components of renin-angiotensin-aldosterone system (RAAS) locally in adipose tissue. Key results: Eplerenone reduced HFD-induced body weight gain, fasting glucose levels, fat accumulation, HFD-induced adipocyte size and liver lipid accumulation and improved glucose tolerance. In the adipose tissue, HFD significantly increased the mRNA levels of the RAAS molecules relative to the ND group. Eplerenone lowered RAAS mRNA levels, components of lipid metabolism and markers of inflammation in HFD-fed animals. Conclusion: MR antagonism with eplerenone diminishes insulin resistance that is related to obesity partly via a reduction of RAAS activation, inflammatory progression and cytokines induction. This suggests that eplerenone should be further studied as a therapeutic option for obesity and overweight. © Copyright © 2020 Vecchiola, Fuentes, Solar, Lagos, Opazo, Muñoz-Durango, Riedel, Owen, Kalergis and Fardella.Ítem Gestational hypothyroxinemia affects its offspring with a reduced suppressive capacity impairing the outcome of the experimental autoimmune encephalomyelitis(Frontiers Media, 2018-06) Haensgen, H.; Albornoz, E.; Opazo, M.C.; Bugueño, K.; Jara Fernández, E.L.; Binzberger, R.; Rivero-Castillo, T.; Venegas Salas, L.F.; Simon, F.; Cabello-Verrugio, C.; Elorza, A.A.; Kalergis, A.M.; Bueno, S.M.; Riedel, C.A.Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such "imprints" on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE. © 2018 Haensgen, Albornoz, Opazo, Bugueño, Jara Fernández, Binzberger, Rivero-Castillo, Venegas Salas, Simon, Cabello-Verrugio, Elorza, Kalergis, Bueno and Riedel.Ítem Heme oxygenase-1 as a modulator of intestinal inflammation development and progression(Frontiers Media S.A., 2018-09) Sebastián, V.P.; Salazar, G.A.; Coronado-Arrázola, I.; Schultz, B.M.; Vallejos, O.P.; Berkowitz, L.; Álvarez-Lobos, M.M.; Riedel, C.A.; Kalergis, A.M.; Bueno, S.M.Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease. © 2018 Sebastián, Salazar, Coronado-Arrázola, Schultz, Vallejos, Berkowitz, álvarez-Lobos, Riedel, Kalergis and Bueno.Ítem Human metapneumovirus: Mechanisms and molecular targets used by the virus to avoid the immune system(Frontiers Media S.A., 2018-10) Soto, J.A.; Gálvez, N.M.S.; Benavente, F.M.; Pizarro-Ortega, M.S.; Lay, M.K.; Riedel, C.; Bueno, S.M.; Gonzalez, P.A.; Kalergis, A.M.Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the Pneumoviridae family and Metapneumovirus genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses. © 2018 Frontiers Media S.A. All rights reserved.Ítem Interleukin-10 Production by T and B Cells Is a Key Factor to Promote Systemic Salmonella enterica Serovar Typhimurium Infection in Mice(Frontiers Media, 2017-08) Salazar, G.A.; Peñaloza, H.F.; Pardo-Roa, C.; Schultz, B.M.; Muñoz-Durango, N.; Gómez, R.S.; Salazar, F.J.; Pizarro, D.P.; Riedel, C.A.; González, P.A.; Alvarez-Lobos, M.; Kalergis, A.M.; Bueno, S.M.Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium that produces disease in numerous hosts. In mice, oral inoculation is followed by intestinal colonization and subsequent systemic dissemination, which leads to severe pathogenesis without the activation of an efficient anti-Salmonella immune response. This feature suggests that the infection caused by S. Typhimurium may promote the production of anti-inflammatory molecules by the host that prevent efficient T cell activation and bacterial clearance. In this study, we describe the contribution of immune cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) to the systemic infection caused by S. Typhimurium in mice. We observed that the production of IL-10 was required by S. Typhimurium to cause a systemic disease, since mice lacking IL-10 (IL-10-/-) were significantly more resistant to die after an infection as compared to wild-type (WT) mice. IL-10-/- mice had reduced bacterial loads in internal organs and increased levels of pro-inflammatory cytokines in serum at 5 days of infection. Importantly, WT mice showed high bacterial loads in tissues and no increase of cytokines in serum after 5 days of S. Typhimurium infection, except for IL-10. In WT mice, we observed a peak of il-10 messenger RNA production in ileum, spleen, and liver after 5 days of infection. Importantly, the adoptive transfer of T or B cells from WT mice restored the susceptibility of IL-10-/- mice to systemic S. Typhimurium infection, suggesting that the generation of regulatory cells in vivo is required to sustain a systemic infection by S. Typhimurium. These findings support the notion that IL-10 production from lymphoid cells is a key process in the infective cycle of S. Typhimurium in mice due to generation of a tolerogenic immune response that prevents bacterial clearance and supports systemic dissemination.Ítem Intestinal microbiota influences non-intestinal related autoimmune diseases(Frontiers Media, 2018-03) Opazo, M.C.; Ortega-Rocha, E.M.; Coronado-Arrázola, I.; Bonifaz, L.C.; Boudin, H.; Neunlist, M.; Bueno, S.M.; Kalergis, A.M.; Riedel, C.A.The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases. © 2018 Opazo, Ortega-Rocha, Coronado-Arrázola, Bonifaz, Boudin, Neunlist, Bueno, Kalergis and Riedel.Ítem Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity(Frontiers Media, 2017-08) Canedo-Marroquín, G.; Acevedo-Acevedo, O.; Rey-Jurado, E.; Saavedra, J.M.; Lay, M.K.; Bueno, S.M.; Riedel, C.A.; Kalergis, A.M.The Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ARTIs) and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F), the Glycoprotein (G), and the Small Hydrophobic (SH) protein, which are located on the virus surface. In addition, the Nucleoprotein (N), Phosphoprotein (P) large polymerase protein (L) part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M) protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2). HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.Ítem Modulation of immunity and inflammation by the Mineralocorticoid receptor and Aldosterone(Hindawi Publishing Corporation, 2015) Muñoz-Durango, N.; Vecchiola, A.; Gonzalez-Gomez, L.M.; Simon, F.; Riedel, C.A.; Fardella, C.E.; Kalergis, A.M.The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models. © 2015 N. Muñoz-Durango et al.Ítem Naturally Derived Heme-Oxygenase 1 Inducers and Their Therapeutic Application to Immune-Mediated Diseases(Frontiers Media S.A., 2020-07) Funes, S.C.; Rios, M.; Fernández-Fierro, A.; Covián, C.; Bueno, S.M.; Riedel, C.A.; Mackern-Oberti, J.P.; Kalergis, A.M.Heme oxygenase (HO) is the primary antioxidant enzyme involved in heme group degradation. A variety of stimuli triggers the expression of the inducible HO-1 isoform, which is modulated by its substrate and cellular stressors. A major anti-inflammatory role has been assigned to the HO-1 activity. Therefore, in recent years HO-1 induction has been employed as an approach to treating several disorders displaying some immune alterations components, such as exacerbated inflammation or self-reactivity. Many natural compounds have shown to be effective inductors of HO-1 without cytotoxic effects; among them, most are chemicals present in plants used as food, flavoring, and medicine. Here we discuss some naturally derived compounds involved in HO-1 induction, their impact in the immune response modulation, and the beneficial effect in diverse autoimmune disorders. We conclude that the use of some compounds from natural sources able to induce HO-1 is an attractive lifestyle toward promoting human health. This review opens a new outlook on the investigation of naturally derived HO-1 inducers, mainly concerning autoimmunity. © Copyright © 2020 Funes, Rios, Fernández-Fierro, Covián, Bueno, Riedel, Mackern-Oberti and Kalergis.Ítem Persistent Salmonella enterica serovar Typhimurium infection increases the susceptibility of mice to develop intestinal inflammation(Frontiers Media, 2018-05) Schultz, B.M.; Salazar, G.A.; Paduro, C.A.; Pardo-Roa, C.; Pizarro, D.P.; Salazar-Echegarai, F.J.; Torres, J.; Riedel, C.A.; Kalergis, A.M.; Alvarez-Lobos, M.M.; Bueno, S.M.Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium (S. Typhimurium) infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S. Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS) and interleukin (IL)-10-/- mice, which develop spontaneous intestinal inflammation. We observed that S. Typhimurium infection makes DSS-treated and IL-10-/- mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S. Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2). Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10-/- mice susceptibility to develop intestinal inflammation due to previous S. Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S. Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2. © 2018 Schultz, Salazar, Paduro, Pardo-Roa, Pizarro, Salazar-Echegarai, Torres, Riedel, Kalergis, álvarez-Lobos and Bueno.