RESUMEN
The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates of the innate and adaptive immune system cells appear in response to an infective or otherwise noxious agent and produce inflammatory mediators. Mediators of inflammation include local and recruited cells and signals. Processes derived from extrinsic and intrinsic CNS diseases also elicit the CNS inflammatory response. A deeper understanding of immune-related inflammation in health and disease is necessary to find potential therapeutic targets for preventing or reducing CNS damage. This review is aimed at discussing the innate and adaptive immune system functions and their roles in regulating brain cell responses in disease and homeostasis maintenance.
Asunto(s)
Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/terapia , Sistema Nervioso Central/fisiología , Neuroinmunomodulación , Enfermedades Neuroinflamatorias/diagnóstico , Enfermedades Neuroinflamatorias/terapia , Inmunidad Adaptativa , Animales , Astrocitos/metabolismo , Autofagia , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Fibrosis , Homeostasis , Humanos , Hipoxia , Sistema Inmunológico/metabolismo , Inflamación , Mediadores de Inflamación/metabolismo , Microglía/metabolismo , Estrés OxidativoRESUMEN
INTRODUCTION: Argentina has been a preferential target for Bolivian immigrants for decades. The relatively recent migratory flux includes Germany, France, the United States, Australia, Japan, and some Latin American countries. The aim of this cross-sectional study was to describe the prevalence of Chagas disease in pregnant women, analyzing the Bolivian-specific Chagas prevalence as the main contributor of migratory populations from Chagas disease-endemic areas to Buenos Aires city, Argentina, and to evaluate the impact of these migrant influxes on the process of the "urbanization" of the disease in reference hospital José Maria Ramos Mejia (JMRM). METHODOLOGY: Overall, 21,332 pregnant women (100%) between 15 and 49 years of age derived from the public maternity service of JMRMH were studied. Serology data was obtained from registered serological diagnosis data, consisting of three different serological tests performed at the Public Parasitology Unit. RESULTS: Although general prevalence decreased during the analyzed period, the specific prevalence of pregnant women from Bolivian origin showed a sustained growth during 1983-2013. Solely 5% of the total pregnant women population from Bolivia contributed to one third of the total Chagas prevalence. CONCLUSIONS: This study showed that a cohort of pregnant women from Bolivia who attended JMRMH during the period 1983-2007 constituted a population at risk for congenital transmission. Increased migration from endemic areas of Bolivia might potentially increase the prevalence of Chagas disease among pregnant women. In addition, this study highlights the importance to analyze specific prevalence according to endemic areas to determine the profiles of potential hidden prevalence.
Asunto(s)
Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/transmisión , Migración Humana , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Argentina/epidemiología , Bolivia/epidemiología , Enfermedad de Chagas/congénito , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Medición de Riesgo , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Serum from asymptomatic or symptomatic (with cardiovascular manifestations) chagasic patients depleted of the complement system displayed an antiproliferative effect on Trypanosoma cruzi epimastigotes, RA strain, when added to the growth medium. This effect was also observed when patient's serum was depleted of specific antibodies. The antiproliferative effect was both time and concentration dependent. It was confined to the non-dialyzable, high molecular weight, fraction of the serum. This effect was abrogated by allopurinol and catalase, and enhanced by N-ethylmaleimide. Xanthine oxidoreductase and xanthine oxidase activities were increased in the chagasic sera, while catalase activity remained unchanged. Parasites exposed to chagasic sera showed a decrease in Fe/superoxide dismutase activity as well as an increase in membrane lipoperoxidation. Our data provides evidence to support the idea that the antiproliferative activity observed in sera from chagasic patients may be due, at least partially, to a direct effect of hydrogen peroxide on the epimastigotes of T. cruzi. The increase of hydrogen peroxide to antiproliferative levels might result from an increase in xanthine oxidase activity in the serum of patients infected with the parasite.
Asunto(s)
Enfermedad de Chagas/inmunología , Suero/inmunología , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/inmunología , Xantina Oxidasa/metabolismo , Adulto , Animales , Antiprotozoarios/metabolismo , Antiprotozoarios/farmacología , Humanos , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Xantina Deshidrogenasa/metabolismoRESUMEN
OBJECTIVE: To assess the importance of B-cell control during parasite infections in multiple sclerosis (MS) patients. METHODS: Peripheral blood CD19+ B cells from 12 helminth-infected MS patients, 12 MS patients without infection, 10 patients infected with Trypanosoma cruzi, 8 subjects infected with Paracoccidioides brasiliensis, and 12 healthy control subjects were purified using magnetic cell sorting. Interleukin (IL)-4, IL-6, IL-10, tumor necrosis factor-alpha, lymphotoxin, transforming growth factor-beta, brain-derived neurotrophic factor, and nerve growth factor secretion were evaluated after stimulation with CDw32 L cells and CD40 antibody using enzyme-linked immunosorbent assays. The production of anti-myelin oligodendrocyte glycoprotein IgG and IgM antibodies was evaluated by enzyme-linked immunosorbent spot assays. Cell phenotype was assessed by flow cytometry. RESULTS: Helminth infections in MS patients created a B-cell population producing high levels of IL-10, dampening harmful immune responses through a mechanism mediated, at least in part, by the ICOS-B7RP-1 pathway. The IL-10-producing B-cell phenotype detected expressed high levels of CD1d and was similar to the one observed in mature naive B2 cells (namely, CD11b(-), CD5(-), CD27(-), and IgD+). Moreover, B cells isolated from helminth-infected MS patients also produced greater amounts of brain-derived neurotrophic factor and nerve growth factor compared with those of normal subjects, T. cruzi-infected subjects, P. brasiliensis-infected subjects, or uninfected MS patients, raising the possibility that these cells may exert a neuroprotective effect on the central nervous system. INTERPRETATION: Increased production of B-cell-derived IL-10 and of neurotrophic factors are part of the parasite's regulation of host immunity and can alter the course of MS, potentially explaining environmental-related MS suppression observed in areas with low disease prevalence.