RESUMEN
INTRODUCTION: Human respiratory syncytial virus (hRSV) is an important cause of lower respiratory tract infections in the pediatric and the geriatric population worldwide. There is a substantial economic burden resulting from hRSV disease during winter. Although no vaccines have been approved for human use, prophylactic therapies are available for high-risk populations. Choosing the proper animal models to evaluate different vaccine prototypes or pharmacological treatments is essential for developing efficient therapies against hRSV. AREAS COVERED: This article describes the relevance of using different animal models to evaluate the effect of antiviral drugs, pharmacological molecules, vaccine prototypes, and antibodies in the protection against hRSV. The animal models covered are rodents, mustelids, bovines, and nonhuman primates. Animals included were chosen based on the available literature and their role in the development of the drugs discussed in this manuscript. EXPERT OPINION: Choosing the correct animal model is critical for exploring and testing treatments that could decrease the impact of hRSV in high-risk populations. Mice will continue to be the most used preclinical model to evaluate this. However, researchers must also explore the use of other models such as nonhuman primates, as they are more similar to humans, prior to escalating into clinical trials.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Anciano , Humanos , Ratones , Animales , Niño , Bovinos , Vacunas contra Virus Sincitial Respiratorio/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Modelos Animales de Enfermedad , Gravedad del PacienteRESUMEN
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.
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Corteza Suprarrenal/inmunología , Aldosterona/inmunología , Inmunomodulación/inmunología , Inflamación/inmunología , Modelos Inmunológicos , Receptores de Mineralocorticoides/inmunología , Animales , Humanos , Factores Inmunológicos/inmunologíaRESUMEN
Despite significant research since it was discovered more than 50 years ago, respiratory syncytial virus (RSV) continues to be the leading agent causing infant hospitalization and respiratory distress worldwide. Although RSV normally does not cause mortality, this virus is recognized as a major public health and economic burden around the globe. RSV can modulate host immunity leading to an inflammatory response that produces lung damage and virus dissemination in the host airways. Remarkably, infection with the virus elicits poor immunity that in most cases fails to protect against subsequent exposures. Here, we review advances made on the understanding of the lifecycle of the virus, some of the molecular mechanisms it has evolved to cause pathology and ineffective immunity during infection. Hopefully, ongoing research will contribute to developing new drugs and candidate vaccines that will decrease the health burden caused by this virus.
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Citocinas/metabolismo , Inmunidad Innata , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/terapia , Citocinas/inmunología , Humanos , Pulmón/inmunología , Pulmón/patología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/patogenicidadRESUMEN
Dendritic cells (DCs) link innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) on bacteria. DCs can capture and degrade bacteria and present their antigens on MHC molecules to T cells. PAMP recognition promotes DC maturation, a phenotypic change that empowers them to prime naïve T cells. As a result, an adaptive immune response that specifically targets bacteria-derived antigens is initiated. Consequently, any impairment of DC function might contribute to bacterial survival and dissemination in the host. Therefore, the characterization of DC-bacteria interactions is required to understand the mechanisms used by virulent bacteria to avoid adaptive immunity. An example of a bacterial pathogen capable of interfering with DC function is Salmonella enterica serovar Typhimurium (S. Typhimurium), which causes a typhoid-like disease in mice. Virulent strains of S. Typhimurium are able to differentially modulate the entrance to DCs and avoid lysosomal degradation, to prevent antigen presentation on MHC molecules. These features of virulent S. Typhimurium are controlled by virulence factors encoded by Salmonella Pathogenicity Islands 1 and 2. Modulation of DC functions by the activity of these gene products is supported by several recent studies, which have shown that pathogenesis might depend on this attribute of virulent S. Typhimurium. Here we discuss recent data showing that several virulence factors from Salmonella are required to differentially modulate DC function and adaptive immunity in the host.
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Células Dendríticas/inmunología , Infecciones por Salmonella/microbiología , Salmonella typhimurium/inmunología , Salmonella typhimurium/patogenicidad , Animales , Humanos , Factores de Virulencia/inmunologíaRESUMEN
Neurological deficits in the offspring caused by human maternal hypothyroxinemia are thought to be irreversible. To understand the mechanism responsible for these neurological alterations, we induced maternal hypothyroxinemia in pregnant rats. Behavior and synapse function were evaluated in the offspring of thyroid hormone-deficient rats. Our data indicate that, when compared with controls, hypothyroxinemic mothers bear litters that, in adulthood, show prolonged latencies during the learning process in the water maze test. Impaired learning capacity caused by hypothyroxinemia was consistent with cellular and molecular alterations, including: 1) lack of increase of phosphorylated c-fos on the second day of the water maze test; 2) impaired induction of long-term potentiation in response to theta-burst stimulation to the Schaffer collateral pathway in the area 1 of the hippocampus Ammon's horn stratum radiatum, despite normal responses for input/output experiments; 3) increase of postsynaptic density protein 95 (PSD-95), N-methyl-D-aspartic acid receptor subunit 1, and tyrosine receptor kinase B levels in brain extracts; and 4) significant increase of PSD-95 at the PSDs and failure of this molecule to colocalize with N-methyl-D-aspartic acid receptor subunit 1, as it was shown by control rats. Our findings suggest that maternal hypothyroxinemia is a harmful condition for the offspring that can affect key molecular components for synaptic function and spatial learning.
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Trastornos del Conocimiento/fisiopatología , Hipotiroidismo/fisiopatología , Aprendizaje por Laberinto/fisiología , Complicaciones del Embarazo/fisiopatología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Tiroxina/deficiencia , Factores de Edad , Animales , Trastornos del Conocimiento/etiología , Homólogo 4 de la Proteína Discs Large , Femenino , Hipotiroidismo/complicaciones , Imidazoles , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Potenciación a Largo Plazo/fisiología , Masculino , Proteínas de la Membrana/metabolismo , Fosforilación , Embarazo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Percepción Espacial/fisiología , Sinapsis/fisiología , Tiroxina/sangreRESUMEN
The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.
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Animales , Humanos , Masculino , Femenino , Isoenzimas/análisis , Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Cutánea/diagnóstico , Brasil , Leishmania braziliensis/enzimología , Leishmaniasis Cutánea/parasitologíaRESUMEN
The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.