RESUMEN
A deficiência de vitamina A (DVA) é um problema de grande interesse em saúde pública, visto que, afecta em todo o mundo, aproximadamente 19 milhões de mulheres grávidas e 190 milhões de crianças em idade pré-escolar, sendo a maioria nas regiões da África e Sudoeste da Ásia (OMS, 2013). Globalmente, estima-se que cerca de 30% das crianças menores de 5 anos de idade sofrem de deficiência de vitamina A, e dois porcentos de todas as mortes em menores de 5 anos de idade são atribuíveis à DVA (Stevens, 2015). Em Moçambique, a deficiência de micronutrientes tais como vitamina A é muito comum e possui alta prevalência em crianças menores de 5 anos e nas suas mães. Um estudo à escala nacional realizado em 2002, mostrou que 69% de crianças menores de 5 anos tinham deficiência de vitamina A (MISAU,2009). Esta condição pode levar a implicações moderadas a graves no sistema visual, tais como: cegueira noturna, xerose conjuntival, mancha de Bitot, xerose corneal, ulceração corneana, queratomalácia e xeroftalmicus (Sarni, Mattos, et al., 2007). Para além disso, consideram-se também como sendo problemas resultantes da DVA: a anemia, a má-resistência a infecções, o elevado risco de doenças e mortes resultantes de infecções na infância, como sarampo e outras doenças causadoras de diarreia (OMS, 2013). A suplementação com vitamina A é actualmente uma das intervenções mais amplamente utilizadas na provisão de vitamina A (Stevens, 2015). Evidências mostram que quando crianças menores de cinco anos são sistematicamente suplementadas com vitamina A pelo menos duas vezes por ano, existe uma contribuição na redução da taxa de mortalidade que varia de 24% a 30% (MISAU, 2018; Beaton et al., 1994). Actualmente, mais de 80 países em todo o mundo, estão a implementar programas de suplementação com vitamina A direccionados a crianças de 6-59 meses de idade (Stevens, 2015). Entre os anos 2003 e 2008, a cobertura de suplementação com vitamina A em Moçambique (uma dose nos últimos seis meses) aumentou consideravelmente de 50% a 72% (MISAU, 2009). O Inquérito Demográfico de Saúde de 2011 indica que a cobertura da suplementação com vitamina A em crianças dos 6 aos 59 meses foi de 78.4% em Nampula, 57.6% na Zambézia, 78.8% em Tete, 91.6% em Manica e 78.7% em Sofala. Verificou-se ainda que cerca de 68% das crianças não escolarizadas foram suplementadas com vitamina A, comparado com 89% das crianças com escolaridade de nível secundário ou mais; sessenta e cinco porcento das crianças no quintil de riqueza mais baixo receberam a suplementação com vitamina A comparado com 90% das crianças no quintil mais elevado (IDS, 2011). Em 1999, a suplementação com vitamina A (SVA) foi inicialmente introduzida em Moçambique através dos Dias Nacionais de Imunização. Em 2002, Moçambique reportou que 69% de crianças menores de 5 anos tinham deficiência de vitamina A. Em 2003, com base nos resultados deste estudo e, reconhecendo a importância da vitamina A na saúde das crianças, sobretudo nos primeiros anos de vida, o Ministério da Saúde em Moçambique introduziu a distribuição de cápsulas de vitamina A através dos serviços de saúde de rotina, à todas as crianças dos 6-59 meses, atingindo taxas de cobertura entre 40 e 60 por cento a nível naciona
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Vitamina A/inmunología , Vacunación Masiva/estadística & datos numéricos , Fenómenos Fisiológicos Nutricionales del Lactante/inmunología , Vacunación Masiva/métodos , Mozambique/epidemiologíaRESUMEN
Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.
Asunto(s)
Inmunidad Innata , Piel/inmunología , Vitamina A/inmunología , Animales , Dermatitis , Humanos , Microbiota/fisiología , Piel/microbiología , Staphylococcus aureus/efectos de los fármacos , Tretinoina , Vitamina A/farmacología , Deficiencia de Vitamina ARESUMEN
BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.
Asunto(s)
Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/prevención & control , Citocinas/inmunología , Pandemias/prevención & control , Neumonía Viral/dietoterapia , Neumonía Viral/prevención & control , Vitaminas/inmunología , Vitaminas/uso terapéutico , Anciano , Ácido Ascórbico/inmunología , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Betacoronavirus/efectos de los fármacos , COVID-19 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Humanos , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Células Th17/efectos de los fármacos , Células Th17/inmunología , Vitamina A/inmunología , Vitamina A/farmacología , Vitamina A/uso terapéutico , Vitamina D/inmunología , Vitamina D/farmacología , Vitamina D/uso terapéutico , Vitamina E/inmunología , Vitamina E/farmacología , Vitamina E/uso terapéutico , Vitaminas/farmacologíaRESUMEN
Questions concerning the influences of nuclear receptors and their ligands on mammalian B cells are vast in number. Here, we briefly review the effects of nuclear receptor ligands, including estrogen and vitamins, on immunoglobulin production and protection from infectious diseases. We describe nuclear receptor interactions with the B cell genome and the potential mechanisms of gene regulation. Attention to the nuclear receptor/ligand regulation of B cell function may help optimize B cell responses, improve pathogen clearance, and prevent damaging responses toward inert- and self-antigens.
Asunto(s)
Linfocitos B/inmunología , Receptores de Esteroides/inmunología , Animales , Linfocitos B/metabolismo , Regulación de la Expresión Génica , Humanos , Inmunidad , Inmunoglobulinas/genética , Inmunoglobulinas/inmunología , Receptores de Esteroides/genética , Hormonas Tiroideas/genética , Hormonas Tiroideas/inmunología , Vitamina A/genética , Vitamina A/inmunología , Vitamina D/genética , Vitamina D/inmunologíaRESUMEN
Vitamin A deficiencies and insufficiencies are widespread in developing countries, and may be gaining prevalence in industrialized nations. To combat vitamin A deficiency (VAD), the World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) in children 6-59 months of age in locations where VAD is endemic. This practice has significantly reduced all-cause death and diarrhea-related mortalities in children, and may have in some cases improved immune responses toward pediatric vaccines. However, VAS studies have yielded conflicting results, perhaps due to influences of baseline vitamin A levels on VAS efficacy, and due to cross-regulation between vitamin A and related nuclear hormones. Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases. We additionally present new results from a VAD mouse model. We found that when VAS was administered to VAD mice at the time of vaccination with a pneumococcal vaccine (Prevnar-13), pneumococcus (T4)-specific antibodies were significantly improved. Preliminary data further showed that after challenge with Streptococcus pneumoniae, all mice that had received VAS at the time of vaccination survived. This was a significant improvement compared to vaccination without VAS. Data encourage renewed attention to vitamin A levels, both in developed and developing countries, to assist interpretation of data from vaccine research and to improve the success of vaccine programs.
Asunto(s)
Inmunogenicidad Vacunal/inmunología , Vitamina A/administración & dosificación , Vitamina A/inmunología , Animales , Suplementos Dietéticos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Vacunas Neumococicas/inmunología , Embarazo , Vacunación/métodos , Deficiencia de Vitamina A/inmunologíaRESUMEN
Diet is an important regulator of the gastrointestinal microbiota. Vitamin A and vitamin D deficiencies result in less diverse, dysbiotic microbial communities and increased susceptibility to infection or injury of the gastrointestinal tract. The vitamin A and vitamin D receptors are nuclear receptors expressed by the host, but not the microbiota. Vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune cells underlies the effects of these nutrients on the microbiota. Vitamin A and vitamin D regulate the expression of tight junction proteins on intestinal epithelial cells that are critical for barrier function in the gut. Other shared functions of vitamin A and vitamin D include the support of innate lymphoid cells that produce IL-22, suppression of IFN-γ and IL-17 by T cells, and induction of regulatory T cells in the mucosal tissues. There are some unique functions of vitamin A and D; for example, vitamin A induces gut homing receptors on T cells, while vitamin D suppresses gut homing receptors on T cells. Together, vitamin A- and vitamin D-mediated regulation of the intestinal epithelium and mucosal immune system shape the microbial communities in the gut to maintain homeostasis.
Asunto(s)
Microbioma Gastrointestinal , Inmunidad Mucosa , Vitamina A/inmunología , Vitamina D/inmunología , Animales , Homeostasis , Humanos , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiologíaRESUMEN
Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.
Asunto(s)
Vacuna BCG/administración & dosificación , Hidrocortisona/metabolismo , Vacuna Antipolio Oral/administración & dosificación , Estrés Psicológico/metabolismo , Toxoide Tetánico/administración & dosificación , Timo/metabolismo , Vitamina A/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Hidrocortisona/inmunología , Lactante , Recién Nacido , Masculino , Estrés Psicológico/inmunología , Linfocitos T/inmunología , Timo/inmunología , Vitamina A/inmunologíaRESUMEN
Background: Asthma is a common childhood disorder with complex pathobiologic components that may include aspects of nutritional deficit. The contribution of vitamin deficiency, specifically vitamin A, as part of the disease complex has not been well studied, particularly among at risk children. In this study, we examined the prevalence of vitamin A as well as zinc deficiency in conjunction with visual function among an urban pediatric population sample with moderate-severe persistent asthma. Methods: A cross-sectional case-control assessment of serum vitamin A, zinc and visual function among urban children with and without asthma was undertaken. Inclusion criteria involved (1) well-controlled pediatric asthmatic patients between the ages of 8-18 with corrected vision of at least 20/25 in each eye and (2) chronic use of a combination beta agonist-steroid inhaler. Visual function was assessed by Snellen visual acuity and Peli Robson contrast sensitivity assessment. Results: Overall, 24 patients were enrolled for study with body mass index and age matched between asthmatic and control groups. Median serum vitamin A and zinc levels among control subjects was statistically higher compared to asthmatics (p = 0.0303 and p = 0.0111, respectively). Based on age-based reference levels there was no evidence of vitamin A or zinc deficiency among asthmatics or controls. Serum vitamin A and zinc were found to directly correlate with body mass index (p = 0.0074 and p = 0.0474, respectively), but not age or measures of visual function. Contrast sensitivity was however significantly reduced among asthmatic subjects (p = 0.0003). Conclusions: Children with chronic asthma demonstrate reduced levels of vitamin A and zinc that may be related to disease pathobiology however, evidence of frank zinc or vitamin A deficiency was not demonstrated. Reduced contrast sensitivity found in the asthmatic group appears unrelated to serum vitamin A and/or zinc levels.
Asunto(s)
Asma/inmunología , Sensibilidad de Contraste/inmunología , Deficiencia de Vitamina A/epidemiología , Vitamina A/inmunología , Zinc/deficiencia , Adolescente , Asma/sangre , Asma/diagnóstico , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Índice de Severidad de la Enfermedad , Vitamina A/sangre , Deficiencia de Vitamina A/sangre , Deficiencia de Vitamina A/diagnóstico , Deficiencia de Vitamina A/inmunología , Zinc/sangre , Zinc/inmunologíaRESUMEN
Previous studies have shown that the interaction between limiting vitamin A (VA) and an alcohol dehydrogenase 1 C (ADH1C) variant in beef cattle results in increased intramuscular fat in the longissimus thoracis muscle in one genotype when fed low dietary VA. Although quality grade is important for increased profitability and improving taste characteristics of beef products, limiting VA too drastically can impair animal welfare. The objectives of this study were to determine if this marker-assisted management strategy would be effective, and whether any impairment in immune function would occur in a feedlot setting. Mixed breed beef steers (n=2000) were sorted into 40 feedlot pens so that all combinations of ADH1C genotype (TT or CT), VA level (50% or 100% of recommended) and hormonal implant status (implanted (IMP) or non-implanted (NI)) were equally represented within the population. The VA×ADH1C interaction was not observed. An implant status × ADH1C interaction was observed with average daily gain (ADG; P=0.03). Steers that were IMP and CT had higher ADG than IMP TT (CT=1.69 and TT=1.62 kg/day), whereas both genotypes in the NI steers were lower (CT=1.29 and TT=1.32 kg/day). Implant status was shown to affect dry matter intake (DMI; IMP=8.55 and NI=7.87 kg; P<0.01), total days-on-feed (IMP=164.4 and NI 210.5 days; P<0.01), USDA yield grade (YIELD; IMP=2.40 and NI=2.77; P<0.01), marbling score (MARB; IMP=392 and NI=455; P<0.01), longissimus thoracis area (LTA; IMP=85.0 and NI=80.7 cm2; P=0.01) and backfat thickness (FAT; IMP=8.0 and NI 10.0 mm; P<0.01). Overall, IMP animals finished on fewer total days-on-feed with higher ADG, DMI, larger LTA, and lower YIELD, MARB and FAT. To investigate immune function parameters, crossbred steers (n=18) were selected from a prior feeding trial so that all combinations of ADH1C (TT, CT and CC) and VA (25% or 75%) were equally represented. Blood cell count analysis and peripheral blood mononuclear cell proliferation and stimulation assays were conducted. None of these immune parameters were affected by VA level. Treatment and mortality records were examined in the 2000 steer population, where no correlations with ADH1C, implant status or VA level were observed. Due to no VA × ADH1C interaction, this nutrigenetic marker-assisted management strategy is not effective at this time in commercial beef cattle feedlots, however, supplementing VA at a level as low as 25% of recommended in finishing rations would likely not result in signs of immune dysfunction.
Asunto(s)
Alcohol Deshidrogenasa/genética , Bovinos/fisiología , Vitamina A/inmunología , Alimentación Animal , Animales , Bovinos/genética , Bovinos/crecimiento & desarrollo , Bovinos/inmunología , Dieta/veterinaria , Genotipo , Leucocitos Mononucleares/inmunología , MasculinoRESUMEN
The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.
Asunto(s)
Trastornos de la Nutrición del Niño/inmunología , Enfermedades Transmisibles/metabolismo , Inmunidad Mucosa , Enfermedades Intestinales/metabolismo , Mucosa Intestinal/metabolismo , Desnutrición/metabolismo , Deficiencia de Vitamina A/metabolismo , Vitamina A/metabolismo , Factores de Edad , Animales , Niño , Trastornos de la Nutrición del Niño/metabolismo , Trastornos de la Nutrición del Niño/fisiopatología , Trastornos de la Nutrición del Niño/terapia , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/fisiopatología , Enfermedades Transmisibles/terapia , Suplementos Dietéticos , Interacciones Huésped-Patógeno , Humanos , Lactante , Enfermedades Intestinales/inmunología , Enfermedades Intestinales/fisiopatología , Enfermedades Intestinales/terapia , Mucosa Intestinal/inmunología , Mucosa Intestinal/fisiopatología , Desnutrición/inmunología , Desnutrición/fisiopatología , Desnutrición/terapia , Estado Nutricional , Permeabilidad , Transducción de Señal , Vitamina A/administración & dosificación , Vitamina A/inmunología , Deficiencia de Vitamina A/inmunología , Deficiencia de Vitamina A/fisiopatología , Deficiencia de Vitamina A/terapiaRESUMEN
High-dose vitamin A supplementation (VAS) may affect mortality to infectious diseases in a sex-differential manner. Here, we analysed the long-term immunological effects of neonatal vitamin A supplementation (NVAS) in 247 children, who had been randomly allocated to 50 000 or 25 000 IU vitamin A (15mg and 7·5mg retinol equivalents, respectively) or placebo at birth. At 4-6 months of age, we assessed bacille Calmette-Guérin (BCG) scarification, and we analysed in vitro responses of TNF-α, IL-5, IL-10, IL-13 and IFN-γ in whole blood stimulations to phytohaemagglutinin (PHA), purified protein derivative (PPD), tetanus toxoid and lipopolysaccharide. There were no differences between the two doses of NVAS, and thus they were analysed combined as NVAS (any dose) v. placebo. All analyses were performed unstratified and by sex. NVAS increased the chance of having a scar after BCG vaccination in females (NVAS v. placebo: 96 v. 71 %, proportion ratio: 1·24; 95 % CI 1·09, 1·42), but not in males (P for interaction=0·012). NVAS was associated with significant sex-differential effects on the pro- to anti-inflammatory cytokine ratios (TNF-α:IL-10) to PPD, tetanus toxoid and medium alone, which were increased in females but decreased in males. In addition, IL-17 responses tended to be increased in NVAS v. placebo recipients in males but not in females, significantly so for the PHA stimulation. The study corroborates sex-differential effects of VAS on the immune system, emphasising the importance of analysing VAS effects by sex.
Asunto(s)
Citocinas/sangre , Suplementos Dietéticos , Factores Sexuales , Vitamina A/administración & dosificación , Vacuna BCG/inmunología , Cicatriz , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Sistema Inmunológico/efectos de los fármacos , Lactante , Masculino , Fitohemaglutininas , Toxoide Tetánico/inmunología , Vacunación , Vitamina A/inmunologíaRESUMEN
Recently, we demonstrated that treatment with all- trans-retinoic acid (tRA) induced a paradoxical effect on immune activation during the development of autoimmune lupus. Here, we further describe its negative effects on mediating neuroinflammation and neurodegeneration. Female MRL/lpr mice were orally administered tRA or VARA (retinol mixed with 10% tRA) from 6 to 14 weeks of age. Both treatments had a significant effect on brain weight, which correlated with histopathological evidence of focal astrogliosis, meningitis, and ventriculitis. Infiltration of CD138- and Iba1-positve immune cells was observed in the third ventricle and meninges of treated mice that co-labeled with ICAM-1, indicating their inflammatory nature. Increased numbers of circulating plasma cells, autoantibodies, and total IgG were also apparent. IgG and C3 complement deposition in these brain regions were also prominent as was focal astrogliosis surrounding the ventricular lining and meninges. Using Fluoro-Jade staining, we further demonstrate that neuroinflammation was accompanied by neurodegeneration in the cortex of treated mice compared with vehicle controls. These findings indicate that vitamin A exposure exacerbates the immunogenic environment of the brain during the onset of systemic autoimmune disease. Vitamin A may therefore compromise the immuno-privileged nature of the central nervous system under a predisposed immunogenic environment.
Asunto(s)
Encéfalo/inmunología , Lupus Eritematoso Sistémico/inmunología , Meningitis/inmunología , Tretinoina/inmunología , Vitamina A/inmunología , Vitaminas/inmunología , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Complemento C3/análisis , Complemento C3/inmunología , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/patología , Meningitis/sangre , Meningitis/patología , Ratones Endogámicos MRL lpr , Tretinoina/administración & dosificación , Vitamina A/administración & dosificación , Vitaminas/administración & dosificaciónRESUMEN
Vitamin A is a multifunctional vitamin implicated in a wide range of biological processes. Its control over the immune system and functions are perhaps the most pleiotropic not only for development but also for the functional fate of almost every cell involved in protective or regulatory adaptive or innate immunity. This is especially key at the intestinal border, where dietary vitamin A is first absorbed. Most effects of vitamin A are exerted by its metabolite, retinoic acid (RA), which through ligation of nuclear receptors controls transcriptional expression of RA target genes. In addition to this canonical function, RA and RA receptors (RARs), either as ligand-receptor or separately, play extranuclear, nongenomic roles that greatly expand the multiple mechanisms employed for their numerous and paradoxical functions that ultimately link environmental sensing with immune cell fate. This review discusses RA and RARs and their complex roles in innate and adaptive immunity.
Asunto(s)
Sistema Inmunológico , Mucosa Intestinal/fisiología , Receptores de Ácido Retinoico/inmunología , Tretinoina/metabolismo , Vitamina A/inmunología , Inmunidad Adaptativa , Animales , Humanos , Inmunidad Innata , Inmunomodulación , Receptores de Ácido Retinoico/metabolismo , Tretinoina/inmunologíaRESUMEN
As vitaminas são compostos orgânicos necessários em poucas quantidades no organismo, todavia indispensáveis para as funções metabólicas. Elas se inserem em inúmeras reações metabólicas, fisiológicas e imunes das células, necessárias para a manutenção da saúde animal, além de atuarem como imunoestimulante. Embora a dieta rica em folhagens verdes frescas forneça quantidades suficientes de vitaminas A, D e E a suplementação intensiva com alimentos conservados na forma de feno ou silagem pode reduzir em até 50 % dos teores destas vitaminas no alimento. Diante disso, a proposta do trabalho foi verificar se a administração parenteral de vitaminas A, D e E age como imunoestimulante em garrotes estabulados e alimentados exclusivamente com feno de tifton. Para tanto 14 bovinos foram divididos em dois grupos homogêneos, sendo o grupo S, suplementado com vitamina A, D e E em dose única de 30 mL por via intramuscular; e o grupo C, sem suplementação. Ambos os grupos foram alojados em baias parcialmente privadas de sol, e alimentados com feno por um período de três meses. A avaliação imune foi realizada por hemogramas e ensaio de função leucocitária (metabolismo oxidativo e fagocitose) nos momentos antes do tratamento, três e dez dias após os tratamentos. Tendo em vista que a suplementação com polivitamínicos A, D e E aumentou a porcentagem da atividade de células granulocítica e a intensidade da atividade de células mononucleares, além de intensificar o efeito antioxidante prolongando a sobrevida de hemácias e neutrófilos, conclui-se que esta suplementação promoveu efeito benéfico na resposta imune de bezerros da Raça Holandesa, apesar dos efeitos deletérios da alimentação exclusiva com feno e da privação parcial da incidência solar direta.
Vitamins are organic compounds which are required in small quantities in the body, however essential for the metabolic functions. They participate in numerous metabolic reactions, physiological and immune cells, needed to maintain animal health, as well as act as immunostimulants. Although the diet rich in fresh green foliage provides sufficient amounts of vitamin A, D and E, intensive supplementation with food stored in the form of hay or silage can reduce up to 50% of the levels of these vitamins in food. Given this, the proposal of this study was to verify how the parenteral administration of vitamins ADE acts as immunostimulant in steers fed exclusively with hay of tifton. For that, 14 cattle were divided into two homogeneous groups: Group S, supplemented with vitamin A, D e E given in a single intramuscular dose of 30mL, and Group C without supplementation. Both groups were housed in private stalls and fed with hay for a period of three months. Immune evaluation was performed by blood count and testing of leukocyte function (oxidative metabolism and phagocytosis) in the moments before treatment, three and ten days after the treatments. Considering that supplementation with vitamin A, D e E increased the percentage of granulocytic cell activity and the intensity of the activity of mononuclear cells, as well as intensified the antioxidant effect prolonging the survival of red blood cells and neutrophils, it can be concluded that this treatment had a beneficial effect on the immune response of Holstein calves, despite the damaging effects of exclusive feeding hay, and the partially deprivation of solar incidence.
Asunto(s)
Animales , Masculino , Bovinos , Cynodon/inmunología , Cynodon/metabolismo , Dieta/veterinaria , Vitaminas en la Dieta/análisis , Especies Reactivas de Oxígeno/análisis , Suplementos Dietéticos/análisis , Vitamina A/inmunología , Vitamina D/inmunología , Vitamina E/inmunologíaRESUMEN
Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this stage of life. Ovalbumin (OVA) was administered orally to mice through breast milk and efficiency of systemic tolerance to OVA was assessed in adulthood using a model of allergic airway inflammation. Oral tolerance induction was fully efficient starting third week of life. Inefficiency in neonates was a consequence of abnormal antigen transfer across the gut barrier and retinaldehyde dehydrogenase expression by mesenteric lymph node CD103(+) neonatal dendritic cells, resulting in inefficient T-cell activation. Neonates' serum retinol levels were three times lower than in adult mice, and vitamin A supplementation was sufficient to rescue neonatal defects and allow tolerance induction from birth. The establishment of oral tolerance required the differentiation of Th1 lymphocytes in both vitamin A-supplemented neonates and 3-week-old unsupplemented mice. This knowledge should guide the design of interventions for allergy prevention that are adapted to the neonatal stage of life such as vitamin A supplementation.
Asunto(s)
Tolerancia Inmunológica/efectos de los fármacos , Ovalbúmina/farmacología , Células TH1/inmunología , Deficiencia de Vitamina A/prevención & control , Vitamina A/administración & dosificación , Administración Oral , Animales , Animales Recién Nacidos , Animales Lactantes , Antígenos CD/genética , Antígenos CD/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Expresión Génica , Cadenas alfa de Integrinas/genética , Cadenas alfa de Integrinas/inmunología , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Activación de Linfocitos , Mesenterio/citología , Mesenterio/inmunología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Células TH1/citología , Vitamina A/inmunología , Vitamina A/metabolismo , Deficiencia de Vitamina A/inmunología , Deficiencia de Vitamina A/fisiopatologíaRESUMEN
Background and Objective: Vitamin A has been linked to the development of allergic diseases although its role is not fully understood, Retinoic acid (RA), a metabolite of Vitamin A, has been previously associated with the prostaglandin pathway, and PTGDR, a receptor of PGD2, has been proposed as a candidate gene in allergy and asthma. Considering the role of PTGDR in allergy, the goal of this study was o analyze the effect of RA on the activation of the promoter region of the PTGDR gene. Methods: A549 lung epithelial cells were transfected with 4 combinations of genetic variants of the PTGDR promoter and stimulated with all-trans RA (ATRA); luciferase assays were performed using the Dual Luciferase Reporter System, and real-time quantitative polymerase chain reaction was used to measure the expression of PTGDR, CYP26A1, RARA, RARB, RARG , and RXRA in basal A549 cell cultures and after ATRA treatment. We also performed an in silico analysis. Results: After ATRA treatment increased expression of CYP26A1 (12-fold) and RARB (4-fold) was detected. ATRA activated PTGDR promoter activity in transfected cells (P<.001) and RA response element sequences were identified in silico in this promoter region. Conclusions: RA modulated PTGDR promoter activity. Differential response to RA and to new treatments based on PTGDR modulation could depend on genetic background in allergic asthmatic patients (AU)
Introducción y Objetivo: La vitamina A se ha relacionado con el desarrollo de las enfermedades alérgicas, si bien su papel no se comprende en su totalidad. El ácido retinoico, un metabolito de la vitamina A, se ha asociado previamente con la ruta de las prostaglandinas. Además, PTGDR, uno de los receptores de PGD2, se ha propuesto como un gen candidato en la alergia y el asma. Considerando el papel de PTGDR en la alergia, el objetivo de este estudio fue analizar el efecto del ácido retinoico sobre la activación de la región promotora del gen PTGDR. Métodos: Se utilizó la línea celular A549 de epitelio de pulmón. Las células fueron transfectadas con cuatro combinaciones de las variantes génicas de PTGDR y fueron estimuladas con ácido retinoico todo-trans (ATRA). Los ensayos de Luciferasa se llevaron a cabo mediante el sistema Dual Luciferase Reporter System. Se realizaron análisis de RT-qPCR para medir la expresión basal de PTGDR, CYP26A1, RARA, RARB, RARG y RXRA de los cultivos de A549 tras el tratamiento con ATRA. Se realizaron también análisis bioinformáticos. Resultados: Se encontraron diferencias significativas en la actividad promotora entre las variantes haplotípicas tras la transfección en la línea celular A549. Tras el tratamiento con ATRA se detectó un incremento de la expresión de CYP26A1 (12 veces) y RARB (4 veces). El ácido retinoico activó la actividad promotora de PTGDR en las células transfectadas (p<0,001). Se identificaron secuencias de Elementos de Respuesta a Ácido Retinoico (RARE) in silico en la región promotora de PTGDR. Conclusiones: El ácido retinoico modula la actividad promotora de PTGDR . Esto podría explicar las diferencias en los efectos del ácido retinoico y en las respuestas a los nuevos tratamientos de la enfermedad alérgica basados en la modulación del receptor PTGDR (AU)
Asunto(s)
Humanos , Masculino , Femenino , Receptores de Ácido Retinoico/análisis , Receptores de Ácido Retinoico/inmunología , Tretinoina/análisis , Tretinoina/inmunología , Vitamina A/análisis , Vitamina A/inmunología , Asma/epidemiología , Asma/inmunología , Luciferasas/análisis , Luciferasas/inmunología , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados/métodosRESUMEN
The effect of vitamin A on mucosal immunity has never been subjected to extensive studies until recently. We started to work in this area in the early 1970s when we observed that children with protein-calorie malnutrition (PCM) often had defective mucosal immunity, judging from the incidence of respiratory tract infections and diarrhea. We reported that these children had depressed secretory IgA (sIgA) levels in their nasal wash fluids. The IgA level in specimens collected from those superimposed with some degrees of vitamin A deficiency state appeared to be more severely affected. In order to better understand the underlying mechanism associated with this condition, we started to study more detail the deficiency state using experimental vitamin A-deficient rats. From a series of experiments using this animal model, we proposed that vitamin A was needed for transport and/or secretion of sIgA across the mucosa. This conclusion was based on the observation that the secretory component of sIgA synthesized by the epithelial cells of these vitamin A deficient animals was adversely affected as compared to the control animals. From that time onward, much progress has been made by several other groups showing that other mechanisms could also influence the integrity and immune function of the mucosa. For instance, recent studies demonstrated that retinoic acid which is a biologically active form of vitamin A has an essential role in mucosal homeostasis, controlling tolerance and immunity in these non-lymphoid tissues. Such a conclusion was made possible by the availability of sophisticated new molecular biology and genetic engineering techniques together with advances in the field of immunoregulation, e.g., the discovery of dendritic cells (DCs) and T helper cell subsets in 1980s, and the role of Toll-like receptors (TLRs) together with other innate immune regulators in controlling adaptive immune response in the early 1990s. These advances provided considerable new insights into the pleiotropic roles of vitamin A including educating mucosal DCs, differentiation of lymphocyte lineages and imprinting them with mucosal-homing properties as well as in regulating tolerance and immunity. The identification of a novel lymphocyte subpopulation, innate lymphoid cells (ILCs), at the beginning of this century has provided us with an additional insight into a new role of vitamin A in regulating homeostasis at the mucosal surface through influencing ILCs. Another new player that regulates intestinal homeostasis and mucosal immune response is microbiota whose composition is known to vary with vitamin A status. So it appears now that the role of vitamin A on mucosal immunity is far beyond regulating the adaptive Th1-Th2 cell response, but is highly pleiotropic and more complicating, e.g., polarizing the phenotype of mucosal DCs and macrophages, directing gut-homing migration of T and B cells, inducing differentiation of effector T cells and Treg subpopulation, balancing mucosal ILCs subpopulation and influencing the composition of microbiota. In this review, I will attempt to bring together these important advances to provide a comprehensive and contemporary perspective on the role of vitamin A in regulating mucosal immunity.
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Enfermedades del Sistema Inmune/inmunología , Inmunidad Mucosa , Desnutrición Proteico-Calórica/inmunología , Deficiencia de Vitamina A/inmunología , Vitamina A/inmunología , Animales , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Microbioma Gastrointestinal/inmunología , Interacciones Huésped-Patógeno , Humanos , Enfermedades del Sistema Inmune/epidemiología , Enfermedades del Sistema Inmune/metabolismo , Enfermedades del Sistema Inmune/microbiología , Inmunoglobulina A Secretora/inmunología , Inmunoglobulina A Secretora/metabolismo , Intestinos/inmunología , Intestinos/microbiología , Estado Nutricional , Fenotipo , Desnutrición Proteico-Calórica/epidemiología , Desnutrición Proteico-Calórica/metabolismo , Desnutrición Proteico-Calórica/microbiología , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Vitamina A/metabolismo , Deficiencia de Vitamina A/epidemiología , Deficiencia de Vitamina A/metabolismo , Deficiencia de Vitamina A/microbiologíaRESUMEN
An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation of regulatory T (Treg) cells. Evidence exists that components in commonly consumed foods including vitamins A, D, and E, water-soluble constituents of mushrooms, polyphenolics in fruits and vegetables, and n-3 fatty acids in fish oil can modulate NK cell activities, Treg cell properties, and the interactions between those two cell types. Thus, it is extremely important for cancer prevention to understand the involvement of dietary components with the early stage dynamics of interactions among these immune cells. This review addresses the potential significance of diet in supporting the function of NK cells, Treg cells, and the balance between those two cell types, which ultimately results in decreased cancer risk.
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Dieta , Células Asesinas Naturales/inmunología , Neoplasias/inmunología , Neoplasias/prevención & control , Linfocitos T Reguladores/inmunología , Animales , Citocinas/inmunología , Ácidos Grasos Omega-3/inmunología , Humanos , Neoplasias/dietoterapia , Polifenoles/inmunología , Vitamina A/inmunología , Vitamina D/inmunologíaRESUMEN
The importance of vitamin A for host defense is undeniable and the study of its mechanisms is paramount. Of the estimated 250 million preschool children who are vitamin A-deficient (VAD), 10% will die from their increased susceptibility to infectious disease. Vitamin A supplementation was established in the 1980s as one of the most successful interventions in the developing world. Understanding how vitamin A controls immunity will help curb the mortality and morbidity associated with vitamin A deficiency and exploit the immune-enhancing capacity of vitamin A to heighten host resistance to infectious disease. The discoveries that retinoic acid (RA) imprints the homing of leukocytes to the gut and enhances the induction of regulatory T cells, highlighted a potential role for RA in mucosal tolerance. However, more recently emerging data tell of a more profound systemic impact of RA on leukocyte function and commitment. In animal models using genetic manipulation of RA signaling, we learned when and how RA controls T cell fate. Here, we review the role for RA as a critical checkpoint regulator in the differentiation of CD4(+) T cells within the immune system.
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Vitamina A/inmunología , Animales , Diferenciación Celular , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunidad Mucosa , Inmunosupresores/uso terapéutico , Inmunoterapia , Ratones , Modelos Inmunológicos , Retinoides/uso terapéutico , Transducción de Señal , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Tretinoina/inmunología , Tretinoina/metabolismo , Deficiencia de Vitamina A/inmunologíaRESUMEN
Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.