RESUMO
Mononuclear cells have been implicated in the primary inflammatory response against mycobacteria. Yet, little is known about the interaction of Mycobacterium bovis bacillus Calmette-Guerin (BCG) with human monocytes. Here, we investigated the potential of BCG Moreau strain to induce in vitro specific cell-death utilizing a flow cytometry approach that revealed an increase in apoptosis events in BCG-stimulated monocytes from healthy adults. We also detected a concomitant release of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), but not metalloproteinase (MMP)-9. In addition, annexin V-propidium iodide double staining demonstrated an enhancement of monocytes necrosis, but not apoptosis, following BCG Moreau strain stimulation of umbilical vein cells from naïve, neonate. This pattern was paralleled by different pro-inflammatory cytokine levels, as well as MMP-9 induction when compared to the adults. Our findings support the hypothesis that BCG induces distinct cell-death patterns during the maturation of the immune system and that this pattern might set the stage for a subsequent antimycobacterial immune response that might have profound effects during vaccination.
Assuntos
Vacina BCG/imunologia , Morte Celular , Interleucina-1beta/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Monócitos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto JovemRESUMO
The current tuberculosis (TB) vaccine Mycobacterium bovis BCG has been employed for some 70 years in Brazil and lessons from its use should be taken in account for the development or improvement of new TB vaccines. The vast majority of the current population has been vaccinated with BCG, with the possible requirement for a booster immunisation in adulthood for TB protection. BCG Moreau strain also protects against leprosy, meningitis and extrapulmonary forms of TB. Factors related to differences in strain, dosage and BCG administering protocol have been responsible for the variable efficacy of BCG. This vaccine is clearly affected by, as yet unclear, host and/or environmental variables. In this brief review, we describe some aspects of BCG immunisation observed in Brazil that may be of importance for improving or replacing BCG.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Tuberculose Pulmonar/prevenção & controle , Brasil , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Imunização Secundária , Saúde da População Rural , Resultado do TratamentoRESUMO
It has been proposed that antigens released by Trypanosoma cruzi sensitize vertebrate cells leading to their destruction by the immune response raised against the parasite. Here, we characterized antigens released by trypomastigotes of T. cruzi that bind to non-infected cells and investigated biological consequences of this adsorption. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of antigens released by [(35)S]-methionine-labeled parasites revealed the presence of polypeptides mainly ranging from 85 to 170 kDa that were specifically recognized by sera from chronically T. cruzi infected rabbits. Polypeptides of 85-110 and 160-170 kDa bound to non-infected epithelial, fibroblast and muscle mammalian cell lines, which thus became targets for anti-T. cruzi antibody binding. Cysteine-proteinase, but not trans-sialidase, was detected among the cell-bound antigens, and purified cysteine-proteinase was adsorbed to non-infected cells. Immunoelectron microscopic studies showed that parasite antigens were mainly released as membrane vesicles that adhered to membrane microvilli and were internalized by mammalian cells. We provide evidence that adsorption of parasite antigens induced an increase in expression of extracellular matrix (ECM) components (fibronectin, laminin and type I collagen) by sensitized cells. Thus, our data reinforce the idea that in vivo T. cruzi released antigens might be involved in the establishment of inflammation, sensitizing non-infected host cells and triggering an immune response against parasite antigens. Further, our data showed that antigen sensitization modulates biological cell functions as ECM expression that could mediate cell-cell or parasite-host cell interactions, contributing to the establishment of inflammation.
Assuntos
Antígenos de Protozoários/imunologia , Antígenos de Protozoários/metabolismo , Antígenos de Superfície/imunologia , Matriz Extracelular/metabolismo , Trypanosoma cruzi/imunologia , Glicoproteínas Variantes de Superfície de Trypanosoma , Adsorção , Animais , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Matriz Extracelular/imunologiaRESUMO
Crianças infectadas pelo HIV-1, por via vertical, apresentam uma evoluçao clínica mais grave do que crianças infectadas por outras vias e adultos. A imaturidade fisiológica dos sistemas imunitários fetal e neonatal, no momento da infecçao, parece ter papel crucial na progressao da infecçao pelo HIV-1 em crianças. Neste artigo, fazemos revisao da ontogenia do sistema imunológico humano, correlacionando-a com a imunopatogenia da síndrome de imunodeficiência adquirida (AIDS), em crianças infectadas por transmissao vertical, em suas diferentes fases.
Assuntos
Humanos , Criança , Lactente , Gravidez , Pré-Escolar , Recém-Nascido , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Formação de Anticorpos , Síndrome da Imunodeficiência Adquirida/transmissão , Síndrome da Imunodeficiência Adquirida/imunologiaRESUMO
The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.
Assuntos
Adulto , Feminino , Humanos , Masculino , Colo do Útero , Técnicas In Vitro , Infecções por HIV/imunologia , Mucosa Intestinal , Tecido Linfoide , Imunidade nas Mucosas , MucosaRESUMO
The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.