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1.
Ann Agric Environ Med ; 26(4): 523-531, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885223

RESUMO

INTRODUCTION: Over 300 species of parasites can possibly be passed on humans. Most of the parasitic infections are defined based on their pathogenicity; however, some positive effects of a parasite existence within the human body have recently been suggested. Beneficial outcomes of parasite infections might result from the production and release of metabolites, modification of host immune response or products uptake of the host. OBJECTIVE: The aim of the study was a comprehensive analysis of a wide range of effects of parasites on the human body, including an overview of the toxic and positive effects. STATE OF KNOWLEDGE: In the light of the latest research presenting the unconventional use of parasites in medicine, the widely understood of their impact on the human body can also be considered in a positive context. Clinical cases from diseases caused by the toxic effects of parasites, as described in recent years, indicate that the problem of parasitic infections still persists. Despite a great deal of knowledge about the toxic effects of parasites on the human organism and, above all, despite the improvement in sanitary conditions, there is a resurgence of parasitic infections, as evidenced, e.g. by the examples presented in this review. CONCLUSIONS: The examples of positive effects of parasites presented so far give hope for the future in terms of fighting many diseases for which pharmacological treatment has not yet brought a positive effect. A better understanding of those processes might lead to the development of new methods of unconventional medical treatment.


Assuntos
Parasitos/química , Doenças Parasitárias/parasitologia , Animais , Humanos , Medicina , Parasitos/metabolismo , Doenças Parasitárias/imunologia
2.
PLoS Negl Trop Dis ; 13(10): e0007776, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31618208

RESUMO

We investigated the impact of helminths and malaria infection on Kaposi's sarcoma associated herpesvirus (KSHV) seropositivity, using samples and data collected from a cluster-randomised trial of intensive versus standard anthelminthic treatment. The trial was carried out in 2012 to 2016 among fishing communities on Lake Victoria islands in Uganda. Plasma samples from 2881 participants from two household surveys, the baseline (1310 participants) and the final (1571 participants) surveys were tested for KSHV IgG antibody responses to K8.1 and ORF73 recombinant proteins using ELISA. The baseline survey was carried out before the trial intervention while the final survey was carried out after three years of the trial intervention. Additionally, a subset sample of 372 participants from the final survey was tested for IgE, IgG and IgG4 antibody concentrations to S. mansoni adults worm antigen (SWA) and S. mansoni egg antigen (SEA) using ELISA. Infection by helminths (S. mansoni, N. americanus, T. trichiura and S. stercoralis) was diagnosed using real-time PCR, urine circulating cathodic antigen (CCA) and stool microscopy (Kato-Katz method) while malaria infection was diagnosed using microscopy. We analysed the relationship between helminth and malaria infections and KSHV seropositivity using regression modelling, allowing for survey design. At baseline, 56% of the participants were male while 48% of the participants were male in the final survey. The most prevalent helminth infection was S. mansoni (at baseline 52% and 34% in the final survey by microscopy, 86% by CCA and 50% by PCR in the final survey). KSHV seropositivity was 66% (baseline) and 56% (final survey) among those 1-12 years and >80% in those 13+ years in both surveys; malaria parasitaemia prevalence was 7% (baseline) and 4% (final survey). At baseline, individuals infected with S. mansoni (detected by microscopy) were more likely to be KSHV seropositive (aOR = 1.86 (1.16, 2.99) p = 0.012) and had higher anti-K8.1 antibody levels (acoefficient = 0.03 (0.01, 0.06) p = 0.02). In the final survey, S. mansoni (by microscopy, adjusted Odds Ratio (aOR = 1.43 (1.04-1.95), p = 0.028) and malaria parasitaemia (aOR = 3.49 (1.08-11.28), p = 0.038) were positively associated with KSHV seropositivity. Additionally, KSHV seropositive participants had higher S. mansoni-specific IgE and IgG antibody concentrations in plasma. Furthermore, HIV infected individuals on cART were less likely to be KSHV seropositive compared to HIV negative individuals (aOR = 0.46 (0.30, 0.71) p = 0.002). Schistosoma species skew the immune response towards Th2 and regulatory responses, which could impact on KSHV reactivation if co-infected with both organisms.


Assuntos
Antígenos de Helmintos/imunologia , Herpesvirus Humano 8/imunologia , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/imunologia , Adolescente , Adulto , Idoso , Albendazol/uso terapêutico , Animais , Anticorpos Anti-Helmínticos/sangue , Criança , Pré-Escolar , Estudos Transversais , Infecções por HIV/imunologia , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintíase/imunologia , Helmintíase/parasitologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Ilhas , Lagos , Malária/imunologia , Pessoa de Meia-Idade , Razão de Chances , Doenças Parasitárias/tratamento farmacológico , Doenças Parasitárias/fisiopatologia , Praziquantel/uso terapêutico , Prevalência , Schistosoma mansoni/imunologia , Esquistossomose mansoni/epidemiologia , Uganda/epidemiologia , Adulto Jovem
3.
Int J Biol Macromol ; 136: 755-763, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220492

RESUMO

Early diagnosis and treatment of parasitic diseases are indispensable to combat parasites mediated morbidity and mortality in humans and animals. Mammalian sourced antibodies are being successfully used in immunotherapy and immunoassays. However, their increased conservation amongst mammals, involves them in unnecessary interaction and immune mediated pathologies, obstructing their applications in certain approaches in immunoassays. Further, the high production cost and difficulty to achieve high and stable antibody titer hampers their utility for therapeutic purposes. In recent years, chicken egg yolk immunoglobulin, termed as immunoglobulin Y (IgY) has attracted noticeable consideration since it poses greater advantages than mammalian IgG including high yield, low cost and convenience. IgY has unique properties which are being exploited in different aspects for its applications in research, diagnosis and therapy. This review gives an overview of the research outcomes pertaining to chicken IgY as diagnostics and therapeutics in parasitology.


Assuntos
Gema de Ovo , Imunoglobulinas/imunologia , Imunoglobulinas/uso terapêutico , Doenças Parasitárias/diagnóstico , Doenças Parasitárias/terapia , Animais , Galinhas , Imunoensaio , Imunoterapia , Doenças Parasitárias/imunologia
4.
Adv Parasitol ; 104: 39-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030771

RESUMO

Humans and animals have co-existed with parasites in a battle of constant adaptation to one another. It is becoming increasingly clear that extracellular vesicles (EVs) play important roles in this co-existence and pathology. This chapter reviews the current research on EVs released by protozoa, nematodes, trematodes, and cestodes with a special focus on EVs in parasite life cycles. The environmental changes experienced by the parasite during its life cycle is associated with distinct changes in EV release and content. The function of these EV seems to have a significant influence on parasite pathology and survival in the host by concomitantly modulating host immune responses and triggering parasite differentiation. The role of EVs in communication between the parasites and the host adds a new level of complexity in our understanding of parasite biology, which may be a key to further understand the complexity behind host-parasite interactions and communication. This increased understanding can, in turn, open up new avenues for vaccine, diagnostic, and therapeutic development for a wide variety of diseases such as parasite infection, cancers, and immunological disorders.


Assuntos
Vesículas Extracelulares/imunologia , Interações Hospedeiro-Parasita , Doenças Parasitárias/imunologia , Animais , Humanos , Doenças Parasitárias/parasitologia
5.
J Immunol Res ; 2019: 3205072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868077

RESUMO

Ficolins are innate pattern recognition receptors (PRR) and play integral roles within the innate immune response to numerous pathogens throughout the circulation, as well as within organs. Pathogens are primarily removed by direct opsonisation following the recognition of cell surface carbohydrates and other immunostimulatory molecules or via the activation of the lectin complement pathway, which results in the deposition of C3b and the recruitment of phagocytes. In recent years, there have been a number of studies implicating ficolins in the recognition and removal of numerous bacterial, viral, fungal, and parasitic pathogens. Moreover, there has been expanding evidence highlighting that mutations within these key immune proteins, or the possession of particular haplotypes, enhance susceptibility to colonization by pathogens and dysfunctional immune responses. This review will therefore encompass previous knowledge on the role of ficolins in the recognition of bacterial and viral pathogens, while acknowledging the recent advances in the immune response to fungal and parasitic infections. Additionally, we will explore the various genetic susceptibility factors that predispose individuals to infection.


Assuntos
Imunidade Inata , Lectinas/genética , Lectinas/imunologia , Polimorfismo de Nucleotídeo Único , Receptores de Reconhecimento de Padrão/imunologia , Animais , Bactérias/imunologia , Bactérias/patogenicidade , Fungos/imunologia , Fungos/patogenicidade , Predisposição Genética para Doença , Humanos , Camundongos , Micoses/imunologia , Parasitos/imunologia , Parasitos/patogenicidade , Doenças Parasitárias/imunologia , Receptores de Reconhecimento de Padrão/genética , Roedores , Vírus/imunologia , Vírus/patogenicidade
6.
Front Immunol ; 10: 212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30815000

RESUMO

The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental identification of host-parasite molecular interactions remains challenging, and the use of computational predictions becomes then necessary. Here, we propose a computational integrative approach to predict host-parasite protein-protein interaction (PPI) networks resulting from the human infection by 15 different eukaryotic parasites. We used an orthology-based approach to transfer high-confidence intraspecies interactions obtained from the STRING database to the corresponding interspecies homolog protein pairs in the host-parasite system. Our approach uses either the parasites predicted secretome and membrane proteins, or only the secretome, depending on whether they are uni- or multi-cellular, respectively, to reduce the number of false predictions. Moreover, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasite growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association with known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. We also provided a study case focusing on a closer examination of the human-S. mansoni predicted interactome, detecting central proteins that have relevant roles in the human-S. mansoni network, and identifying tissue-specific interactions with key roles in the life cycle of the parasite. The predicted PPI networks can be visualized and downloaded at http://orthohpi.jensenlab.org.


Assuntos
Interações Hospedeiro-Parasita , Parasitos/fisiologia , Doenças Parasitárias/parasitologia , Animais , Biologia Computacional/métodos , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Modelos Biológicos , Doenças Parasitárias/genética , Doenças Parasitárias/imunologia , Doenças Parasitárias/metabolismo , Mapeamento de Interação de Proteínas , Proteínas de Protozoários/metabolismo
7.
PLoS Negl Trop Dis ; 13(2): e0007172, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30818339

RESUMO

BACKGROUND: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy. METHODOLOGY/PRINCIPAL FINDINGS: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups. CONCLUSIONS/SIGNIFICANCE: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.


Assuntos
Anticorpos Antibacterianos/sangue , Doenças Parasitárias/imunologia , Complicações Parasitárias na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Adulto , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Estudos de Coortes , Difteria/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche/uso terapêutico , Feminino , Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae tipo b , Vacinas contra Hepatite B/uso terapêutico , Humanos , Lactente , Doenças Parasitárias/tratamento farmacológico , Vacinas Pneumocócicas/uso terapêutico , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/parasitologia , Estudos Prospectivos , Streptococcus pneumoniae , Tétano/prevenção & controle , Vacinação , Coqueluche/prevenção & controle , Adulto Jovem
8.
Parasite Immunol ; 41(6): e12588, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30188574

RESUMO

Brazil is a middle-income country undergoing the epidemiological transition. Effects of changes in daily life habits and access to clean water, sanitation and urban services on a growing urban population have contributed to a double burden of both infectious and noncommunicable chronic diseases. Studies have indicated that parasite infections may modulate the human immune system and influence the development of allergic conditions such as asthma. However, there is no consensus in the published literature on the effects of parasitic infections on allergy, perhaps as a consequence of factors determining the epidemiology of these infections that vary between populations such as age of first infection, duration and chronicity of infections, parasite burden and species, and host genetic susceptibility. In this review, we discuss the observations from Brazil concerning the relationship between parasite infections and allergy.


Assuntos
Hipersensibilidade/imunologia , Parasitos/imunologia , Doenças Parasitárias/imunologia , Animais , Brasil , Humanos , Hipersensibilidade/parasitologia , Estudos Observacionais como Assunto , Doenças Parasitárias/parasitologia
9.
Dev Comp Immunol ; 90: 90-99, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30205126

RESUMO

In vertebrates, the T cell receptor (TCR) plays a crucial role in immune system. To date, the roles of fish TCRs in response to pathogen infection are still poorly understood. In the present study, we firstly cloned and identified the TCRα and TCRß from dojo loach (Misgurnus anguillicaudatus) by RACE approaches. The full-length cDNAs of Ma-TCRα and Ma-TCRß include an open reading frame (ORF) of 723 and 879 bp encoding a polypeptide of 241 and 293 amino acids, respectively. Structural analysis indicated that Ma-TCRα and Ma-TCRß had a signal peptide, IgV domain, IgC domain, a connecting peptide (CPS), a transmembrane region (TM) and a cytoplasmic (CYT), which are similar to their counterparts described in other teleost. Phylogenetic analysis supported that Ma-TCR Cα and Ma-TCR Cß were closely related to the Cα and Cß region of Cyprinidae family, respectively. Transcriptional expression analysis indicated that Ma-TCRα and Ma-TCRß mRNAs were ubiquitously expressed in a wide array of tissues and most abundantly found in skin, brain, kidney, gill and spleen. The expression patterns of Ma-TCRα and Ma-TCRß after bacteria (F. columnare G4), parasite (Ichthyophthirius multifiliis) and fungus (Saprolegnia) infection were detected by qRT-PCR. Additionally, the morphological changes of gill and skin following the three infection models were investigated. The results clearly indicated that Ma-TCRα and Ma-TCRß was significant up-regulated not only in spleen and kidney, but also in skin and gill. In summary, our present findings suggested that Ma-TCRα and Ma-TCRß might play significantly roles in the modulation of immune response and protect loach from different pathogens infection.


Assuntos
Infecções Bacterianas/imunologia , Cyprinidae/genética , Cipriniformes/imunologia , Micoses/imunologia , Doenças Parasitárias/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Saprolegnia/fisiologia , Animais , Clonagem Molecular , Regulação da Expressão Gênica , Filogenia , Transcriptoma
10.
Cancer Immunol Immunother ; 68(5): 823-833, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30302498

RESUMO

Eosinophils are a subset of granulocytes mostly known for their ability to combat parasites and induce allergy. Although they were described to be related to cancer more than 100 years ago, their role in tumors is still undefined. Recent observations revealed that they display regulatory functions towards other immune cell subsets in the tumor microenvironment or direct cytotoxic functions against tumor cells, leading to either antitumor or protumor effects. This paradoxical role of eosinophils was suggested to be dependent on the different factors in the TME. In addition, the clinical relevance of these cells has been recently addressed. In most cases, the accumulation of eosinophils both in the tumor tissue, called tumor-associated tissue eosinophilia, and in the peripheral blood were reported to be prognostic markers for a better outcome of cancer patients. In immunotherapy of cancer, particularly in therapy with immune checkpoint inhibitors, eosinophils were even shown to be a potential predictive marker for a beneficial clinical response. A better understanding of their role in cancer progression will help to establish them as prognostic and predictive markers and to design strategies for targeting eosinophils.


Assuntos
Eosinófilos/imunologia , Hipersensibilidade/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Doenças Parasitárias/imunologia , Biomarcadores , Citotoxicidade Imunológica , Humanos , Prognóstico , Microambiente Tumoral
11.
Front Immunol ; 9: 2579, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30467504

RESUMO

Parasites have evolved a wide range of mechanisms that they use to evade or manipulate the host's immune response and establish infection. The majority of the in vivo studies that have investigated these host-parasite interactions have been undertaken in experimental animals, especially rodents, which were housed and maintained to a high microbiological status. However, in the field situation it is increasingly apparent that pathogen co-infections within the same host are a common occurrence. For example, chronic infection with pathogens including malarial parasites, soil-transmitted helminths, Mycobacterium tuberculosis and viruses such as HIV may affect a third of the human population of some developing countries. Increasing evidence shows that co-infection with these pathogens may alter susceptibility to other important pathogens, and/or influence vaccine efficacy through their effects on host immune responsiveness. Co-infection with certain pathogens may also hinder accurate disease diagnosis. This review summarizes our current understanding of how the host's immune response to infection with different types of parasites can influence susceptibility to infection with other pathogenic microorganisms. A greater understanding of how infectious disease susceptibility and pathogenesis can be influenced by parasite co-infections will enhance disease diagnosis and the design of novel vaccines or therapeutics to more effectively control the spread of infectious diseases.


Assuntos
Coinfecção/imunologia , Parasitos/imunologia , Doenças Parasitárias/imunologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Interações Hospedeiro-Parasita , Humanos , Camundongos , Ratos
12.
PLoS Pathog ; 14(11): e1007251, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30395648

RESUMO

The olfactory organ of vertebrates receives chemical cues present in the air or water and, at the same time, they are exposed to invading pathogens. Nasal-associated lymphoid tissue (NALT), which serves as a mucosal inductive site for humoral immune responses against antigen stimulation in mammals, is present also in teleosts. IgT in teleosts is responsible for similar functions to those carried out by IgA in mammals. Moreover, teleost NALT is known to contain B-cells and teleost nasal mucus contains immunoglobulins (Igs). Yet, whether nasal B cells and Igs respond to infection remains unknown. We hypothesized that water-borne parasites can invade the nasal cavity of fish and elicit local specific immune responses. To address this hypothesis, we developed a model of bath infection with the Ichthyophthirius multifiliis (Ich) parasite in rainbow trout, Oncorhynchus mykiss, an ancient bony fish, and investigated the nasal adaptive immune response against this parasite. Critically, we found that Ich parasites in water could reach the nasal cavity and successfully invade the nasal mucosa. Moreover, strong parasite-specific IgT responses were detected in the nasal mucus, and the accumulation of IgT+ B-cells was noted in the nasal epidermis after Ich infection. Strikingly, local IgT+ B-cell proliferation and parasite-specific IgT generation were found in the trout olfactory organ, providing new evidence that nasal-specific immune responses were induced locally by a parasitic challenge. Overall, our findings suggest that nasal mucosal adaptive immune responses are similar to those reported in other fish mucosal sites and that an antibody system with a dedicated mucosal Ig performs evolutionary conserved functions across vertebrate mucosal surfaces.


Assuntos
Imunidade nas Mucosas/imunologia , Cavidade Nasal/imunologia , Oncorhynchus mykiss/imunologia , Imunidade Adaptativa/imunologia , Animais , Linfócitos B/imunologia , Doenças Transmissíveis , Doenças dos Peixes/imunologia , Peixes/imunologia , Imunidade Humoral , Imunoglobulinas/imunologia , Tecido Linfoide/imunologia , Mucosa Nasal/imunologia , Doenças Parasitárias/imunologia , Doenças Parasitárias/prevenção & controle
13.
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30177522

RESUMO

The mammalian gut is a remarkable organ: with a nervous system that rivals the spinal cord, it is the body's largest repository of immune and endocrine cells and houses an immense and complex microbiota. Infection with helminth parasites elicits a conserved program of effector and regulatory immune responses to eradicate the worm, limit tissue damage, and return the gut to homeostasis. Discrete changes in the nervous system, and to a lesser extent the enteroendocrine system, occur following helminth infection but the importance of these adaptations in expelling the worm is poorly understood. Approximately 90% of the body's serotonin (5-hydroxytryptamine (5-HT)) is made in enterochromaffin (EC) cells in the gut, indicative of the importance of this amine in intestinal function. Signaling via a plethora of receptor subtypes, substantial evidence illustrates that 5-HT affects immunity. A small number of studies document changes in 5-HT levels following infection with helminth parasites, but these have not been complemented by an understanding of the role of 5-HT in the host-parasite interaction. In reviewing this area, the gap in knowledge of how changes in the enteric serotonergic system affects the outcome of infection with intestinal helminths is apparent. We present this as a call-to-action by investigators in the field. We contend that neuronal EC cell-immune interactions in the gut are essential in maintaining homeostasis and, when perturbed, contribute to pathophysiology. The full affect of infection with helminth parasites needs to define, and then mechanistically dissect the role of the enteric nervous and enteroendocrine systems of the gut.


Assuntos
Imunidade Inata , Intestinos/imunologia , Doenças Parasitárias/imunologia , Serotonina/imunologia , Animais , Células Enterocromafins/imunologia , Células Enterocromafins/metabolismo , Microbioma Gastrointestinal/imunologia , Helmintos/imunologia , Helmintos/patogenicidade , Humanos , Intestinos/microbiologia , Intestinos/parasitologia , Sistema Nervoso/imunologia , Doenças Parasitárias/parasitologia , Receptores de Serotonina/genética , Serotonina/metabolismo , Transdução de Sinais
14.
J Leukoc Biol ; 104(6): 1069-1085, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30145844

RESUMO

Acquired and genetic immunodeficiencies have revealed an indispensable role for CD4+ T cells in the induction of protective host immune responses against a myriad of microbial pathogens. Influenced by the cytokines present in the microenvironment, activated CD4+ T cells may differentiate into several highly-specialized helper subsets defined by the production of distinct signature cytokines tailored to combat diverse classes of pathogens. The process of specification and differentiation is controlled by networks of core, master, and accessory transcription factors, which ensure that CD4+ T helper (TH ) cell responses mounted against an invading microbe are of the correct specificity and type. However, aberrant activation or inactivation of transcription factors can result in sustained and elevated expression of immune-related genes, leading to chronic activation of CD4+ TH  cells and organ-specific autoimmunity. In this review, we provide an overview of the molecular basis of CD4+ TH  cell differentiation and examine how combinatorial expression of transcription factors, which promotes genetic plasticity of CD4+ TH  cells, can contribute to immunological dysfunction of CD4+ TH responses. We also discuss recent studies which highlight the potential of exploiting the genetic plasticity of CD4+ TH  cells in the treatment of autoimmune and other immune-mediated disorders.


Assuntos
Inflamação/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Transcrição Genética , Animais , Asma/imunologia , Doenças Autoimunes/imunologia , Regulação da Expressão Gênica , Humanos , Hipersensibilidade/imunologia , Inflamação/genética , Ativação Linfocitária , Camundongos , Doenças Parasitárias/imunologia , Fatores de Transcrição/fisiologia
15.
Microbiol Immunol ; 62(8): 485-496, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29998521

RESUMO

A diverse population of regulatory B (Breg) cells reportedly exhibits significant immunomodulatory effects in various models of inflammatory responses and infectious diseases caused by bacteria, viruses or parasites. Breg cells contribute to maintenance of homeostasis via IL-10 production and multiple IL-10-independent mechanisms. The current review describes various phenotypic and functional subsets of Breg cells in autoimmune and infectious diseases and discusses the impacts of experimental conditions that have been found to drive Breg cell differentiation.


Assuntos
Linfócitos B Reguladores/imunologia , Interleucina-10/imunologia , Fenótipo , Animais , Doenças Autoimunes/imunologia , Linfócitos B , Infecções Bacterianas/imunologia , Diferenciação Celular/imunologia , Doenças Transmissíveis/imunologia , Humanos , Fatores Imunológicos/imunologia , Doenças Parasitárias/imunologia , Viroses/imunologia
16.
J Leukoc Biol ; 104(4): 729-735, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30020539

RESUMO

Guanylate-binding proteins (GBPs) are conserved family of IFN-inducible GTPases that play an important role in the host immunity against bacterial, viral, and protozoan pathogens. GBPs protect the host by associating with intracellular microbes, their vacuolar niche or, in the case of viruses, with their replication complex. This association results in a restriction of the respective pathogen, yet the exact molecular mechanisms of the antimicrobial functions of GBPs are still unclear. Recent work has linked the GBPs with the activation of inflammasomes, multi-protein complexes that assemble upon recognition of pathogen- or host-derived signals and that drive the release of cytokines and host cell death. Here, we will focus on the most recent findings that have started to unravel the manifold restriction mechanism controlled by GBPs in mouse and human cells, and that shed light on the molecular cues that control GBP recruitment to bacterial membranes.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , Imunidade Inata , /imunologia , Animais , Infecções Bacterianas/enzimologia , Infecções Bacterianas/imunologia , Caspases/fisiologia , Membrana Celular/metabolismo , Citocinas/metabolismo , Humanos , Inflamassomos/imunologia , Lipopolissacarídeos/metabolismo , Mamíferos/imunologia , Camundongos , Doenças Parasitárias/enzimologia , Doenças Parasitárias/imunologia , Transporte Proteico , Infecções por Protozoários/enzimologia , Infecções por Protozoários/imunologia , Viroses/enzimologia , Viroses/imunologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-29868503

RESUMO

Deficiency of leptin (ob/ob) and/or desensitization of leptin signaling (db/db) and elevated expression of suppressor of cytokine signaling-3 (SOCS3) reported in obesity are also reported in a variety of pathologies including hypertriglyceridemia, insulin resistance, and malnutrition as the risk factors in host defense system. Viral infections cause the elevated SOCS3 expression, which inhibits leptin signaling. It results in immunosuppression by T-regulatory cells (Tregs). The host immunity becomes incompetent to manage pathogens' attack and invasion, which results in the accelerated infections and diminished vaccine-specific antibody response. Leptin was successfully used as mucosal vaccine adjuvant against Rhodococcus equi. Leptin induced the antibody response to Helicobacter pylori vaccination in mice. An integral leptin signaling in mucosal gut epithelial cells offered resistance against Clostridium difficile and Entameoba histolytica infections. We present in this review, the intervention of leptin in lethal diseases caused by microbial infections and propose the possible scope and challenges of leptin as an adjuvant tool in the development of effective vaccines.


Assuntos
Adjuvantes Imunológicos , Imunidade , Leptina/imunologia , Leptina/farmacologia , Vacinas , Infecções por Actinomycetales/imunologia , Infecções por Actinomycetales/prevenção & controle , Animais , Infecções por Clostridium/imunologia , Clostridium difficile , Citocinas/metabolismo , Células Epiteliais/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Hipertrigliceridemia , Imunidade nas Mucosas/efeitos dos fármacos , Resistência à Insulina , Desnutrição , Camundongos , Obesidade , Doenças Parasitárias/imunologia , Fagocitose/efeitos dos fármacos , Rhodococcus equi , Fatores de Risco , Sepse/imunologia , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Vacinação , Viroses/imunologia
18.
Biomol Concepts ; 9(1): 64-79, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29856726

RESUMO

A key player in driving cellular immunity, IFN-γ is capable of orchestrating numerous protective functions to heighten immune responses in infections and cancers. It can exhibit its immunomodulatory effects by enhancing antigen processing and presentation, increasing leukocyte trafficking, inducing an anti-viral state, boosting the anti-microbial functions and affecting cellular proliferation and apoptosis. A complex interplay between immune cell activity and IFN-γ through coordinated integration of signals from other pathways involving cytokines and Pattern Recognition Receptors (PRRs) such as Interleukin (IL)-4, TNF-α, Lipopolysaccharide (LPS), Type-I Interferons (IFNS) etc. leads to initiation of a cascade of pro-inflammatory responses. Microarray data has unraveled numerous genes whose transcriptional regulation is influenced by IFN-γ. Consequently, IFN-γ stimulated cells display altered expression of many such target genes which mediate its downstream effector functions. The importance of IFN-γ is further reinforced by the fact that mice possessing disruptions in the IFN-γ gene or its receptor develop extreme susceptibility to infectious diseases and rapidly succumb to them. In this review, we attempt to elucidate the biological functions and physiological importance of this versatile cytokine. The functional implications of its biological activity in several infectious diseases and autoimmune pathologies are also discussed. As a counter strategy, many virulent pathogenic species have devised ways to thwart IFN-γ endowed immune-protection. Thus, IFN-γ mediated host-pathogen interactions are critical for our understanding of disease mechanisms and these aspects also manifest enormous therapeutic importance for the annulment of various infections and autoimmune conditions.


Assuntos
Doenças Transmissíveis/imunologia , Interferon gama/fisiologia , Animais , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/metabolismo , Citocinas/fisiologia , Regulação da Expressão Gênica , Humanos , Interferon gama/metabolismo , Interferon gama/uso terapêutico , Listeriose/imunologia , Camundongos , Infecções por Mycobacterium/imunologia , Doenças Parasitárias/imunologia , Ratos , Infecções por Salmonella/imunologia
20.
HLA ; 91(4): 255-270, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29368453

RESUMO

Little attention has been devoted to the role of HLA-G gene and molecule on parasitic disorders, and the available studies have focused on malaria, African and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis. After reporting a brief description regarding the role of the cells of innate and adaptive immune system against parasites, we reviewed the major features of the HLA-G gene and molecule and the role of HLA-G on the major cells of immune system. Increased levels of soluble HLA-G (sHLA-G) have been observed in patients presenting toxoplasmosis and in the active phase of echinococcosis. In addition, increased sHLA-G has also been associated with increased susceptibility to malaria and increased susceptibility to develop human African trypanosomiasis (HAT). In contrast, decreased membrane-bound HLA-G has been reported in placenta of patients infected with Plasmodium falciparum and in heart and colon of patients presenting Chagas disease. The 3' untranslated region of the HLA-G gene has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting distinct patterns of associations. Considering that HLA-G is an immune checkpoint molecule, inhibiting the activity of several cells of the immune system, the excessive neoexpression and the increased sHLA-G levels together with the decreased constitutive tissue expression of membrane-bound HLA-G may be detrimental to the host infected with parasite agents.


Assuntos
Antígenos HLA-G/metabolismo , Doenças Parasitárias/imunologia , Antígenos HLA-G/genética , Humanos , Sistema Imunitário/parasitologia , Imunidade
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