RESUMO
The trypanosomatid pathogens Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, currently grouped as TriTryps, have evolved through the time to overcome the upfront innate immune response and establish the infection in humans adapting many aspects of the parasite-cell host interaction. Extracellular vesicles (EVs) emerge as critical structures carrying different key molecules from parasites and target cells that interact continuously during infection. Current information regarding the structure and composition of these vesicles provide new insights into the primary role of TriTryps-EVs reviewed in this work. Expanding knowledge about these critical vesicular structures will promote advances in basic sciences and in translational applications controlling pathogenesis in the neglected tropical diseases caused by TriTryps.
Assuntos
Vesículas Extracelulares/imunologia , Leishmania major/imunologia , Infecções por Protozoários/imunologia , Trypanosoma brucei brucei/imunologia , Trypanosoma cruzi/imunologia , Animais , Vesículas Extracelulares/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunidade Inata/imunologia , Infecções por Protozoários/parasitologiaRESUMO
Inflammasomes are cytosolic complexes that assemble in response to cellular stress or upon sensing microbial molecules, culminating in cytokine processing and an inflammatory form of cell death called pyroptosis. Inflammasomes are usually composed of a sensor molecule, an adaptor protein, and an inflammatory caspase, such as Caspase-1, which cleaves and activates multiple substrates, including Gasdermin-D, pro-IL-1ß, and pro-IL-18. Ultimately, inflammasome activation promotes inflammation and restriction of the microbial infection. In recent years, many studies have addressed the role of inflammasomes during fungal, bacterial, viral, and parasitic diseases, revealing sophisticated aspects of the host-pathogen interaction. In this review, we summarize recent advances on inflammasome activation in response to intracellular parasites, including Leishmania spp., Plasmodium spp., Trypanosoma cruzi, and Toxoplasma gondii.
Assuntos
Interações Hospedeiro-Patógeno/imunologia , Inflamassomos/imunologia , Infecções por Protozoários/imunologia , Animais , Eucariotos/imunologia , Humanos , Leishmaniose/imunologia , Leishmaniose/parasitologia , Malária/imunologia , Malária/parasitologia , Infecções por Protozoários/parasitologia , Pesquisa/tendências , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Tripanossomíase/imunologia , Tripanossomíase/parasitologiaAssuntos
Infecções por Protozoários/tratamento farmacológico , Infecções por Protozoários/imunologia , Infecções por Protozoários/prevenção & controle , Antiprotozoários/uso terapêutico , Interações Hospedeiro-Parasita/imunologia , Humanos , Malária/tratamento farmacológico , Malária/imunologia , Malária/prevenção & controle , Plasmodium , Vacinas Protozoárias , Trypanosoma , Tripanossomíase/tratamento farmacológico , Tripanossomíase/imunologia , Tripanossomíase/prevenção & controleRESUMO
The peritoneal cavity has a microenvironment capable of promoting proliferation, differentiation, and activation of the resident cells and recruitment of blood cells through the capillary network involved in the peritoneum. Among the cells found in the peritoneal cavity, B-1 cells are a particular cell type that contains features that are not very well defined. These cells differ from conventional B lymphocytes (B-2) by phenotypic, functional, and molecular characteristics. B-1 cells can produce natural antibodies, migrate to the inflammatory focus, and have the ability to phagocytose pathogens. However, the role of B-1 cells in immunity against parasites is still not completely understood. Several experimental models have demonstrated that B-1 cells can affect the susceptibility or resistance to parasite infections depending on the model and species. Here, we review the literature to provide information on the peculiarities of B-1 lymphocytes as well as their interaction with parasites.
Assuntos
Subpopulações de Linfócitos B/imunologia , Helmintíase/imunologia , Helmintos/imunologia , Imunidade Humoral/imunologia , Parasitos/imunologia , Cavidade Peritoneal/citologia , Infecções por Protozoários/imunologia , Animais , Citocinas/biossíntese , Citocinas/imunologia , Helmintíase/parasitologia , Humanos , Camundongos , Peritônio/citologia , Peritônio/imunologia , Infecções por Protozoários/parasitologiaRESUMO
In biology, models are experimental systems meant to recreate aspects of diseases or human tissue with the goal of generating inferences and approximations that can contribute to the resolution of specific biological problems. Although there are many models for studying intracellular parasites, their data have produced critical contradictions, especially in immunological assays. Peripheral blood mononuclear cells (PBMCs) represent an attractive tissue source in pharmacogenomics and in molecular and immunologic studies, as these cells are easily collected from patients and can serve as sentinel tissue for monitoring physiological perturbations due to disease. However, these cells are a very sensitive model due to variables such as temperature, type of stimulus and time of collection as part of posterior processes. PBMCs have been used to study Toxoplasma gondii and other apicomplexan parasites. For instance, this model is frequently used in new therapies or vaccines that use peptides or recombinant proteins derived from the parasite. The immune response to T. gondii is highly variable, so it may be necessary to refine this cellular model. This mini review highlights the major approaches in which PBMCs are used as a model of study for T. gondii and other apicomplexan parasites. The variables related to this model have significant implications for data interpretation and conclusions related to host-parasite interaction.
Assuntos
Apicomplexa/crescimento & desenvolvimento , Apicomplexa/imunologia , Interações Hospedeiro-Patógeno , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/parasitologia , Modelos Teóricos , Infecções por Protozoários/fisiopatologia , Animais , Pesquisa Biomédica/tendências , Humanos , Infecções por Protozoários/imunologia , Infecções por Protozoários/parasitologiaRESUMO
Lipid droplets (lipid bodies, LDs) are dynamic organelles that have important roles in regulating lipid metabolism, energy homeostasis, cell signaling, membrane trafficking, and inflammation. LD biogenesis, composition, and functions are highly regulated and may vary according to the stimuli, cell type, activation state, and inflammatory environment. Increased cytoplasmic LDs are frequently observed in leukocytes and other cells in a number of infectious diseases. Accumulating evidence reveals LDs participation in fundamental mechanisms of host-pathogen interactions, including cell signaling and immunity. LDs are sources of eicosanoid production, and may participate in different aspects of innate signaling and antigen presentation. In addition, intracellular pathogens evolved mechanisms to subvert host metabolism and may use host LDs, as ways of immune evasion and nutrients source. Here, we review mechanisms of LDs biogenesis and their contributions to the infection progress, and discuss the latest discoveries on mechanisms and pathways involving LDs roles as regulators of the immune response to protozoan infection.
Assuntos
Interações Hospedeiro-Parasita , Gotículas Lipídicas/imunologia , Metabolismo dos Lipídeos , Lipídeos/biossíntese , Biogênese de Organelas , Animais , Apresentação de Antígeno , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Transporte Proteico , Infecções por Protozoários/imunologia , Transdução de Sinais/imunologiaRESUMO
The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases. In some cases, the related selenocysteine was incorporated at selected proteins. In invertebrate parasites, antioxidant systems have evolved in a diversity of both substrates and enzymes, representing a potential area in the design of anti-parasite strategies. The present review focus on the organization of the thiol-based antioxidant systems in invertebrate parasites. Differences between these taxa and its final mammal host is stressed. An understanding of the antioxidant defense mechanisms in this kind of parasites, as well as their interactions with the specific host is crucial in the design of drugs targeting these organisms.
Assuntos
Antioxidantes/metabolismo , Infecções por Protozoários/parasitologia , Compostos de Sulfidrila/metabolismo , Animais , Entamoeba/imunologia , Entamoeba/metabolismo , Interações Hospedeiro-Parasita , Humanos , Imunidade Inata , Plasmodium/imunologia , Plasmodium/metabolismo , Infecções por Protozoários/imunologia , Schistosoma/imunologia , Schistosoma/metabolismo , Taenia/imunologia , Taenia/metabolismoRESUMO
The human gut is a highly complex ecosystem with an extensive microbial community, and the influence of the intestinal microbiota reaches the entire host organism. For example, the microbiome regulates fat storage, stimulates or renews epithelial cells, and influences the development and maturation of the brain and the immune system. Intestinal microbes can protect against infection by pathogenic bacteria, viruses, fungi and parasites. Hence, the maintenance of homeostasis between the gut microbiota and the rest of the body is crucial for health, with dysbiosis affecting disease. This review focuses on intestinal protozoa, especially those still representing a public health problem in Mexico, and their interactions with the microbiome and the host. The decrease in prevalence of intestinal helminthes in humans left a vacant ecological niche that was quickly occupied by protozoa. Although the mechanisms governing the interaction between intestinal microbiota and protozoa are poorly understood, it is known that the composition of the intestinal bacterial populations modulates the progression of protozoan infection and the outcome of parasitic disease. Most reports on the complex interactions between intestinal bacteria, protozoa and the immune system emphasize the protective role of the microbiota against protozoan infection. Insights into such protection may facilitate the manipulation of microbiota components to prevent and treat intestinal protozoan infections. Here we discuss recent findings about the immunoregulatory effect of intestinal microbiota with regards to intestinal colonization by protozoa, focusing on infections by Entamoeba histolytica, Blastocystis spp, Giardia duodenalis, Toxoplasma gondii and Cryptosporidium parvum. The possible consequences of the microbiota on parasitic, allergic and autoimmune disorders are also considered.
Assuntos
Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Parasitos/imunologia , Parasitos/microbiologia , Infecções por Protozoários/etiologia , Animais , Disbiose/microbiologia , Disbiose/parasitologia , Homeostase , Humanos , México , Infecções por Protozoários/imunologia , Infecções por Protozoários/microbiologiaRESUMO
Inflammasomes are multimeric complexes of proteins that are assembled in the host cell cytoplasm in response to specific stress signals or contamination of the cytoplasm by microbial molecules. The canonical inflammasomes are composed of at least three main components: an inflammatory caspase (caspase-1, caspase-11), an adapter molecule (such as ASC), and a sensor protein (such as NLRP1, NLRP3, NLRP12, NAIP1, NAIP2, NAIP5, or AIM2). The sensor molecule determines the inflammasome specificity by detecting specific microbial products or cell stress signals. Upon activation, these molecular platforms facilitate restriction of microbial replication and trigger an inflammatory form of cell death called pyroptosis, thus accounting for the genesis of inflammatory processes. Inflammasome activation has been widely reported in response to pathogenic bacteria. However, recent reports have highlighted the important role of the inflammasomes in the host response to the pathogenesis of infections caused by intracellular protozoan parasites. Herein, we review the activation and specific roles of inflammasomes in recognition and host responses to intracellular protozoan parasites such as Trypanosoma cruzi, Toxoplasma gondii, Plasmodium spp., and Leishmania spp.
Assuntos
Inflamassomos/metabolismo , Complexos Multiproteicos/metabolismo , Infecções por Protozoários/imunologia , Animais , Humanos , Imunidade Inata , Inflamassomos/imunologia , Complexos Multiproteicos/imunologia , Piroptose , Receptores de Reconhecimento de Padrão , Transdução de SinaisRESUMO
The lectin pathway of the complement system has a pivotal role in the defense against infectious organisms. After binding of mannan-binding lectin (MBL), ficolins or collectin 11 to carbohydrates or acetylated residues on pathogen surfaces, dimers of MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2) activate a proteolytic cascade, which culminates in the formation of the membrane attack complex and pathogen lysis. Alternative splicing of the pre-mRNA encoding MASP-1 results in two other products, MASP-3 and MAp44, which regulate activation of the cascade. A similar mechanism allows the gene encoding MASP-2 to produce the truncated MAp19 protein. Polymorphisms in MASP1 and MASP2 genes are associated with protein serum levels and functional activity. Since the first report of a MASP deficiency in 2003, deficiencies in lectin pathway proteins have been associated with recurrent infections and several polymorphisms were associated with the susceptibility or protection to infectious diseases. In this review, we summarize the findings on the role of MASP polymorphisms and serum levels in bacterial, viral and protozoan infectious diseases.
Assuntos
Infecções Bacterianas/imunologia , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Infecções por Protozoários/imunologia , Viroses/imunologia , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Lectina de Ligação a Manose da Via do Complemento/genética , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologia , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Polimorfismo Genético , Infecções por Protozoários/genética , Infecções por Protozoários/parasitologia , Infecções por Protozoários/patologia , Transdução de Sinais , Viroses/genética , Viroses/patologia , Viroses/virologiaRESUMO
The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50=10nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound.
Assuntos
Antiprotozoários/farmacologia , Infecções por Protozoários/imunologia , Tiazóis/química , Animais , Desenho de Fármacos , HumanosRESUMO
This study aimed to measure the levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate (NO x ) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-γ, TNF-α, IL-1, IL-6, and NO x . Cytokines were assessed by ELISA quantitative sandwich technique, and NO x was measured by the modified Griess method. Cytokine levels (IFN-γ, TNF-α, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of NO x were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.
Assuntos
Citocinas/sangue , Óxido Nítrico/sangue , Piroplasmida/imunologia , Infecções por Protozoários/imunologia , Animais , Técnicas de Química Analítica , Modelos Animais de Doenças , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Protozoários/parasitologia , Infecções por Protozoários/patologia , Soro/químicaRESUMO
BACKGROUND: Early wheezing and asthma are relevant health problems in the tropics. Mite sensitization is an important risk factor, but the roles of others, inherent in poverty, are unknown. We designed a birth-cohort study in Cartagena (Colombia) to investigate genetic and environmental risk factors for asthma and atopy, considering as particular features perennial exposure to mites, parasite infections and poor living conditions. METHODS: Pregnant women representative of the low-income suburbs of the city were randomly screened for eligibility at delivery; 326 mother-infant pairs were included at baseline and biological samples were collected from birth to 24 months for immunological testing, molecular genetics and gene expression analysis. Pre and post-natal information was collected using questionnaires. RESULTS: 94% of families were from the poorest communes of the city, 40% lacked sewage and 11% tap-water. Intestinal parasites were found as early as 3 months; by the second year, 37.9% of children have had parasites and 5.22% detectable eggs of Ascaris lumbricoides in stools (Median 3458 epg, IQR 975-9256). The prevalence of "wheezing ever" was 17.5% at 6 months, 31.1% at 12 months and 38.3% at 24 months; and recurrent wheezing (3 or more episodes) 7.1% at 12 months and 14.2% at 24 months. Maternal rhinitis [aOR 3.03 (95%CI 1.60-5.74), p = 0.001] and male gender [aOR 2.09 (95%CI 1.09 - 4.01), p = 0.026], increased risk for wheezing at 6 months. At 24 months, maternal asthma was the main predisposing factor for wheezing [aOR 3.65 (95%CI 1.23-10.8), p = 0.01]. Clinical symptoms of milk/egg allergy or other food-induced allergies were scarce (1.8%) and no case of atopic eczema was observed. CONCLUSIONS: Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. At 24 months, the natural history of allergic symptoms is different to the "atopic march" described in some industrialized countries. This cohort is representative of socially deprived urban areas of underdeveloped tropical countries. The collection of biological samples, data on exposure and defined phenotypes, will contribute to understand the gene/environment interactions leading to allergy inception and evolution.
Assuntos
Eczema/epidemiologia , Eczema/etiologia , Pobreza , Sons Respiratórios/etiologia , Sons Respiratórios/imunologia , Clima Tropical , População Urbana , Adolescente , Adulto , Animais , Asma/epidemiologia , Asma/imunologia , Pré-Escolar , Estudos de Coortes , Colômbia/epidemiologia , Eczema/imunologia , Feminino , Habitação , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/imunologia , Gravidez , Prevalência , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/imunologia , Rinite Alérgica Perene/imunologia , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
Os protozoários Neospora caninum e N. hughesi infectam os equinos e podem provocar diferentes sinais clínicos associados a problemas reprodutivos ou a distúrbios neurológicos, respectivamente. A patogenia da neosporose é pouco conhecida nos equinos, bem como as fontes de infecção horizontal de N. hughesi. Além disso, há dúvidas quanto ao papel da transmissão vertical de Neospora spp. na sua manutenção em populações equinas. Neste estudo avaliaram-se: (1) a ocorrência da infecção por Neospora spp. na população de éguas em idade reprodutiva em um haras de cavalos da raça Crioula; e (2) a possível associação entre o status sorológico destas éguas com o de suas crias, como meio de investigar, indiretamente, a relevância da transmissão transplacentária na ocorrência da infecção por Neospora spp. nestes animais. A associação entre o status sorológico das éguas e o de suas crias foi altamente significativa. Os animais descendentes de éguas soropositivas tiveram maior ocorrência de anticorpos anti-Neospora spp. do que os descendentes de éguas soronegativas, embora expostos aos mesmos fatores de risco ambientais. A associação entre parentesco em primeiro grau e status sorológico indica a influência da infecção vertical (transplacentária) na ocorrência de Neospora spp. na população equina estudada.
Neospora caninum and N. hughesi are protozoa which can infect horses and can cause reproductive and neurological diseases, respectively. The pathogenesis of neosporosis in horses is poorly understood, as well as the sources of horizontal infection of N. hughesi. Furthermore, there are doubts about the role of the vertical transmission of Neospora spp. in maintenance of these parasites in equine populations. In this study, we evaluated: (1) the occurrence of infections by Neospora spp. in a population of mares (in reproductive age) on a farm of Crioula breed horses; and (2) the possible association between the serological status of mares and of their offspring, aiming to investigate, indirectly, the relevance of transplacental transmission for the occurrence of Neospora spp. in these horses. We found a highly significant association between the serological status of mares and their offspring. Although had been exposed to the same environmental risk factors, the descendants of seropositive mares had a higher percentage of seropositivity against Neospora spp. compared to the descendants of seronegative mares. The association between kinship and serological status indicates an influence of vertical (transplacental) infection raising the occurrence of Neospora spp. in the studied equine population.
Assuntos
Animais , Feminino , Gravidez , Anticorpos Antiprotozoários/efeitos adversos , Diagnóstico/análise , Infecções por Protozoários/imunologia , Infecções por Protozoários/patologia , Infecções por Protozoários/transmissão , Reprodução/imunologia , Testes Sorológicos/métodos , Testes Sorológicos/veterinária , Relações Materno-Fetais , Transmissão Vertical de Doenças Infecciosas/veterináriaRESUMO
Os protozoários Neospora caninum e N. hughesi infectam os equinos e podem provocar diferentes sinais clínicos associados a problemas reprodutivos ou a distúrbios neurológicos, respectivamente. A patogenia da neosporose é pouco conhecida nos equinos, bem como as fontes de infecção horizontal de N. hughesi. Além disso, há dúvidas quanto ao papel da transmissão vertical de Neospora spp. na sua manutenção em populações equinas. Neste estudo avaliaram-se: (1) a ocorrência da infecção por Neospora spp. na população de éguas em idade reprodutiva em um haras de cavalos da raça Crioula; e (2) a possível associação entre o status sorológico destas éguas com o de suas crias, como meio de investigar, indiretamente, a relevância da transmissão transplacentária na ocorrência da infecção por Neospora spp. nestes animais. A associação entre o status sorológico das éguas e o de suas crias foi altamente significativa. Os animais descendentes de éguas soropositivas tiveram maior ocorrência de anticorpos anti-Neospora spp. do que os descendentes de éguas soronegativas, embora expostos aos mesmos fatores de risco ambientais. A associação entre parentesco em primeiro grau e status sorológico indica a influência da infecção vertical (transplacentária) na ocorrência de Neospora spp. na população equina estudada.(AU)
Neospora caninum and N. hughesi are protozoa which can infect horses and can cause reproductive and neurological diseases, respectively. The pathogenesis of neosporosis in horses is poorly understood, as well as the sources of horizontal infection of N. hughesi. Furthermore, there are doubts about the role of the vertical transmission of Neospora spp. in maintenance of these parasites in equine populations. In this study, we evaluated: (1) the occurrence of infections by Neospora spp. in a population of mares (in reproductive age) on a farm of Crioula breed horses; and (2) the possible association between the serological status of mares and of their offspring, aiming to investigate, indirectly, the relevance of transplacental transmission for the occurrence of Neospora spp. in these horses. We found a highly significant association between the serological status of mares and their offspring. Although had been exposed to the same environmental risk factors, the descendants of seropositive mares had a higher percentage of seropositivity against Neospora spp. compared to the descendants of seronegative mares. The association between kinship and serological status indicates an influence of vertical (transplacental) infection raising the occurrence of Neospora spp. in the studied equine population.(AU)
Assuntos
Animais , Feminino , Gravidez , Infecções por Protozoários/imunologia , Infecções por Protozoários/patologia , Infecções por Protozoários/transmissão , Reprodução/imunologia , Anticorpos Antiprotozoários/efeitos adversos , Diagnóstico/análise , Testes Sorológicos/métodos , Transmissão Vertical de Doenças Infecciosas/veterinária , Relações Materno-FetaisRESUMO
Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.
Assuntos
Humanos , Helmintíase/imunologia , Óxido Nítrico Sintase/imunologia , Óxido Nítrico/imunologia , Infecções por Protozoários/imunologia , Óxido Nítrico Sintase Tipo I/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo III/imunologia , Regulação para Cima/imunologiaRESUMO
Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.
Assuntos
Helmintíase/imunologia , Óxido Nítrico Sintase/imunologia , Óxido Nítrico/imunologia , Infecções por Protozoários/imunologia , Humanos , Óxido Nítrico Sintase Tipo I/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo III/imunologia , Regulação para Cima/imunologiaRESUMO
Caspases are cysteine aspartases acting either as initiators (caspases 8, 9, and 10) or executioners (caspases 3, 6, and 7) to induce programmed cell death by apoptosis. Parasite infections by certain intracellular protozoans increase host cell life span by targeting caspase activation. Conversely, caspase activation, followed by apoptosis of lymphocytes and other cells, prevents effective immune responses to chronic parasite infection. Here we discuss how pharmacological inhibition of caspases might affect the immunity to protozoan infections, by either blocking or delaying apoptosis.