RESUMO
Immunosuppressed patients, particularly transplant recipients, can develop severe strongyloidiasis. This study aimed to detect anti-Strongyloides IgG antibodies in a panel of sera from liver transplant patients. Two techniques were used: ELISA as the initial screening test and Western blotting as a confirmatory test. ELISA reactivity of 10.9% (32/294) was observed. The 40-30 kDa fraction was recognised in 93.7% (30/32) of the patients, resulting in a positivity rate of 10.2%. These data highlight the importance of serological screening for Strongyloides stercoralis infection in liver transplant recipients.
Assuntos
Anticorpos Anti-Helmínticos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Transplante de Fígado , Strongyloides stercoralis , Estrongiloidíase , Transplantados , Humanos , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Estrongiloidíase/sangue , Anticorpos Anti-Helmínticos/sangue , Animais , Strongyloides stercoralis/imunologia , Imunoglobulina G/sangue , Western Blotting , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Feminino , Adulto , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/imunologia , Hospedeiro Imunocomprometido , IdosoRESUMO
The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.
Assuntos
Eosinófilos/imunologia , Imunidade/imunologia , Hepatopatias/imunologia , Fígado/imunologia , Doenças Negligenciadas/imunologia , Esquistossomose mansoni/imunologia , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/parasitologia , Feminino , Fibrose/imunologia , Fibrose/parasitologia , Granuloma/imunologia , Granuloma/parasitologia , Intestinos/imunologia , Intestinos/parasitologia , Fígado/parasitologia , Hepatopatias/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Doenças Negligenciadas/parasitologiaRESUMO
Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.
Assuntos
Antígenos de Helmintos/administração & dosagem , Ascaríase/prevenção & controle , Ascaris suum/imunologia , Doenças Negligenciadas/prevenção & controle , Vacinas Protozoárias/administração & dosagem , Animais , Antígenos de Helmintos/imunologia , Ascaríase/imunologia , Ascaríase/parasitologia , Ascaríase/patologia , Ascaris suum/isolamento & purificação , Feminino , Humanos , Pulmão/imunologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/patologia , Vacinas Protozoárias/imunologia , Células Th2/imunologia , Eficácia de Vacinas , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.
Assuntos
Doenças Endêmicas , Proteínas de Helminto/fisiologia , Helmintíase/epidemiologia , Sistema Imunitário/parasitologia , Doenças Negligenciadas/parasitologia , Animais , Região do Caribe/epidemiologia , Gerenciamento Clínico , Helmintíase/imunologia , Helmintíase/parasitologia , Interações Hospedeiro-Parasita , Humanos , América Latina/epidemiologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/imunologia , Medicina TropicalRESUMO
Purinergic receptors are widespread in the human organism and are involved in several physiological functions like neurotransmission, nociception, platelet aggregation, etc. In the immune system, they may regulate the expression and release of pro-inflammatory factors as well as the activation and death of several cell types. It is already described the participation of some purinergic receptors in the inflammation and pathological processes, such as a few neglected tropical diseases (NTDs) which affect more than 1 billion people in the world. Although the high social influence those diseases represent endemic countries, most of them do not have an efficient, safe or affordable drug treatment. In that way, this review aims to discuss the current literature involving purinergic receptor and immune response to NTDs pathogens, which may contribute in the search for new therapeutic possibilities.
Assuntos
Doenças Negligenciadas/tratamento farmacológico , Receptores Purinérgicos/metabolismo , Medicina Tropical/métodos , Animais , Humanos , Imunidade , Inflamação , Terapia de Alvo Molecular/métodos , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections. First, we predicted the theoretical secretome shared by the three tapeworms starting from their full reported proteomes. Then, through immunoinformatics, we identified proteins within the shared secretome displaying high antigenicity scores and bearing T cell epitopes able to bind most human MHC-II alleles. Secondly, in such proteins, we identified linear B cell epitopes without post-translational modifications, and mapped them on 3D modelled structures to visualize their antibody accessibilities. As a result, we finally suggested two antigenic peptides shared between the secretomes of the three parasite species, which could be further tested for their immunodiagnostic potential.
Assuntos
Biologia Computacional/métodos , Echinococcus/isolamento & purificação , Helmintíase/diagnóstico , Peptídeos/metabolismo , Taenia/isolamento & purificação , Animais , Anticorpos Anti-Helmínticos/metabolismo , Antígenos de Helmintos/imunologia , Echinococcus/metabolismo , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Genoma Helmíntico , Proteínas de Helminto/imunologia , Proteínas de Helminto/metabolismo , Helmintíase/imunologia , Helmintíase/parasitologia , Humanos , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/parasitologia , Processamento de Proteína Pós-Traducional , Proteoma/imunologia , Proteoma/metabolismo , Taenia/metabolismoRESUMO
BACKGROUND: Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. METHODS/PRINCIPAL FINDINGS: We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman's rho = 0.75). In both high- and low transmission settings, mean antibody curves revealed changes in population mean antibody levels that were masked by seroprevalence measures because changes took place above or below the seropositivity cutoff. CONCLUSIONS/SIGNIFICANCE: Age-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. Our results suggest quantitative antibody levels will be particularly useful to measure differences in exposure for pathogens that elicit a transient antibody response or for monitoring populations with very high- or very low transmission, when seroprevalence is less informative. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets.
Assuntos
Anticorpos/sangue , Filariose Linfática/epidemiologia , Gastroenteropatias/epidemiologia , Malária/epidemiologia , Doenças Negligenciadas/epidemiologia , Testes Sorológicos/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Estudos Transversais , Filariose Linfática/imunologia , Feminino , Gastroenteropatias/imunologia , Haiti/epidemiologia , Humanos , Lactente , Recém-Nascido , Malária/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/imunologia , Nigéria/epidemiologia , Polinésia/epidemiologia , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following characteristics are associated with this disease: (i) traumatic inoculation by implantation from an environmental source, leading to an initial cutaneous lesion at the inoculation site; (ii) chronic and progressive cutaneous and subcutaneous tissular involvement associated with fibrotic and granulomatous reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral involvement; and (iv) the presence of muriform (sclerotic) cells embedded in the affected tissue. CBM lesions are clinically polymorphic and are commonly misdiagnosed as various other infectious and noninfectious diseases. In its more severe clinical forms, CBM may cause an incapacity for labor due to fibrotic sequelae and also due to a series of clinical complications, and if not recognized at an early stage, this disease can be refractory to antifungal therapy.
Assuntos
Cromoblastomicose/epidemiologia , Exophiala/classificação , Doenças Profissionais/microbiologia , Antifúngicos/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/imunologia , Gerenciamento Clínico , Farmacorresistência Fúngica Múltipla , Humanos , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/microbiologia , Doenças Profissionais/epidemiologia , FilogeniaRESUMO
Cysticercosis is an infection caused by the metacestode larval stage of Taenia parasites in tissues and elicits a host-parasite reaction in which the immune response may be decisive in the disease development. The aim of this study was to evaluate the role of IFNγ (IFN-gamma) in the experimental model of subcutaneous infection with Taenia crassiceps (T. crassiceps) cysticerci using IFNγ knockout mice. Male C57BL/6 and C57BL/6 KO IFNγ mice 8-12 weeks of age were inoculated with T. crassiceps cysticerci into the subcutaneous tissue of the dorsum. At 7 and 30 (acute phase), 60 and 90 (chronic phase) days post infection, animals from each group had their blood and the subcutaneous tissues collected for serologic and pathological studies. IFNγ and IL-4 were dosed and the histopathological analysis was performed. In the presence of IFNγ there was the establishment of a mixed Th1/Th2 systemic immune profile. This profile also locally induced the granuloma formation which was constituted by cells that played important roles in the parasitary destruction and that were likely associated to the Th1 axis of mixed immune response. On the other hand, the absence of IFNγ appears to favor the parasitary growth which may be related to the development of a systemic Th2 immune response. This profile influenced the granuloma formation with immunoregulatory properties and appears to be important in the collagen synthesis.
Assuntos
Cisticercose/imunologia , Cysticercus/imunologia , Granuloma/imunologia , Interferon gama/imunologia , Animais , Cisticercose/classificação , Cisticercose/patologia , Modelos Animais de Doenças , Granuloma/classificação , Granuloma/patologia , Interações Hospedeiro-Parasita/imunologia , Interferon gama/sangue , Interleucina-4/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças Negligenciadas/classificação , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/patologia , Fatores de TempoRESUMO
Strongyloidiasis is one of the major intestinal infections in humans, and a neglected tropical disease whose diagnosis still poses a challenge. We hypothesized that diagnostic tests based on short peptides containing major epitopes may represent a promising strategy to improve strongyloidiasis detection due to reduced cross-reactivity and higher sensitivity. Our aim was to evaluate two synthetic peptides selected by phage display (C10 and D3) as potential tools for serodiagnosis of strongyloidiasis, and to predict their putative antigen target. To investigate their diagnostic potential, we have tested different panels of serum samples (n=120) by enzyme linked immunosorbent assay (ELISA) to detect specific IgG, and their diagnostic parameters were calculated. Similarities with proteins from Strongyloides stercoralis were searched and conformational epitopes were predicted and aligned to known protein structures. Both C10 and D3 achieved sensitivity of 95%, and specificities were 89.2% and 92.5%, respectively. D3 presented the highest diagnostic efficiency (93.3%). Epitope prediction for both C10 and D3 led to the alignment with the cytochrome c oxidase subunit 1 structure. In brief, we propose two synthetic peptides as new biomarkers for serodiagnosis of strongyloidiasis, which can be promptly used for ELISA and in future field sensor platforms.
Assuntos
Epitopos de Linfócito B/imunologia , Doenças Negligenciadas/imunologia , Fragmentos de Peptídeos/imunologia , Strongyloides stercoralis/imunologia , Estrongiloidíase/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Biomarcadores/metabolismo , Brasil , Simulação por Computador , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Humanos , Fragmentos de Peptídeos/síntese química , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Testes Sorológicos/métodosRESUMO
Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management.
Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/patologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/patologia , Trypanosoma cruzi/isolamento & purificação , Doença de Chagas/imunologia , Saúde Global , Humanos , Doenças Negligenciadas/imunologia , Recidiva , Topografia Médica , Trypanosoma cruzi/imunologiaRESUMO
Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Resistência à Doença/imunologia , Esquistossomose/imunologia , Vacinas/imunologia , Adolescente , Adulto , Anticorpos Anti-Helmínticos/imunologia , Brasil/epidemiologia , Doença Crônica , Análise por Conglomerados , Doenças Endêmicas , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/imunologia , Análise Serial de Proteínas , Esquistossomose/sangue , Esquistossomose/epidemiologia , Adulto JovemRESUMO
Leprosy is an ancient disease that remains endemic and continues to be a major public health problem in some tropical countries, where it has been internationally recognized as being linked to the underdevelopment conditions. The natural course of the disease covers a wide variety of clinical conditions with systemic involvement. In this paper, we review the findings obtained in studies of the pathological mechanisms of leprosy, including a survey of the literature and of our own work. The understanding and control of the wide variety of clinical conditions should help improve patient care and thus prevent the onset of physical impairment and the stigma of the disease.
Assuntos
Feminino , Humanos , Masculino , Hanseníase , Doenças Negligenciadas , Hanseníase/complicações , Hanseníase/imunologia , Hanseníase/metabolismo , Hanseníase/patologia , Doenças Negligenciadas/complicações , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/metabolismo , Doenças Negligenciadas/patologia , Estigma Social , Clima TropicalRESUMO
Neglected tropical diseases (NTDs) impair the lives of 1 billion people worldwide, and threaten the health of millions more. Although vaccine candidates have been proposed to prevent some NTDs, no vaccine is available at the market yet. Vaccines against NTDs should be low-cost and needle-free to reduce the logistic cost of their administration. Plant-based vaccines meet both requirements: plant systems allow antigen production at low cost, and also yield an optimal delivery vehicle that prevents or delays digestive hydrolysis of vaccine antigens. This review covers recent reports on the development of plant-based vaccines against NTDs. Efforts conducted by a number of research groups to develop vaccines as a mean to fight rabies, cysticercosis, dengue, and helminthiasis are emphasized. Future perspectives are identified, such as the need to develop vaccination models for more than ten pathologies through a plant-based biotechnological approach. Current limitations on the method are also noted, and molecular approaches that might allow us to address such limitations are discussed.
Assuntos
Doenças Negligenciadas/imunologia , Medicina Tropical/métodos , Vacinas/química , Países em Desenvolvimento , Humanos , Doenças Negligenciadas/prevenção & controle , Plantas Geneticamente Modificadas , Vacinas/economia , Vacinas/uso terapêuticoRESUMO
Leprosy is an ancient disease that remains endemic and continues to be a major public health problem in some tropical countries, where it has been internationally recognized as being linked to the underdevelopment conditions. The natural course of the disease covers a wide variety of clinical conditions with systemic involvement. In this paper, we review the findings obtained in studies of the pathological mechanisms of leprosy, including a survey of the literature and of our own work. The understanding and control of the wide variety of clinical conditions should help improve patient care and thus prevent the onset of physical impairment and the stigma of the disease.