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1.
Parasit Vectors ; 17(1): 208, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720313

RESUMO

BACKGROUND: Triatoma infestans, Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius prolixus are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Chickens serve as an important blood food source for triatomines. This study aimed to assess the insecticidal activity of fluralaner (Exzolt®) administered to chickens against triatomines (R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata). METHODS: Twelve non-breed chickens (Gallus gallus domesticus) were randomized based on weight into three groups: negative control (n = 4); a single dose of 0.5 mg/kg fluralaner (Exzolt®) (n = 4); two doses of 0.5 mg/kg fluralaner (Exzolt®) (n = 4). Nymphs of 3rd, 4th and 5th instars of R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata (all n = 10) were allowed to feed on chickens before treatment, and at intervals of 1, 7, 14, 21, 28, 35 and 56 days after treatment, with insect mortality determined. RESULTS: Treatment with two doses of fluralaner showed higher insecticidal efficacy against R. prolixus, T. infestans and T. brasiliensis compared to the single-dose treatment. Similar insecticidal efficacy was observed for T. pseudomaculata for one and two doses of fluralaner. Insecticidal activity of fluralaner (Exzolt®) against triatomine bugs was noted up to 21 and 28 days after treatment with one and two doses of fluralaner, respectively. CONCLUSIONS: The results demonstrate that treatment of chickens with fluralaner (Exzolt®) induces insecticidal activity against triatomines for up to 28 days post-treatment, suggesting its potential use as a control strategy for Chagas disease in endemic areas.


Assuntos
Galinhas , Inseticidas , Isoxazóis , Animais , Galinhas/parasitologia , Isoxazóis/farmacologia , Isoxazóis/administração & dosagem , Inseticidas/farmacologia , Inseticidas/administração & dosagem , Insetos Vetores/efeitos dos fármacos , Doença de Chagas/transmissão , Doença de Chagas/tratamento farmacológico , Doença de Chagas/veterinária , Triatominae , Ninfa/efeitos dos fármacos , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Triatoma/efeitos dos fármacos
2.
Viruses ; 15(9)2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37766239

RESUMO

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFNγ and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols.


Assuntos
Hipersensibilidade , Microcefalia , Infecção por Zika virus , Zika virus , Criança , Humanos , Quimiocina CCL2 , Hipersensibilidade/complicações , Hipersensibilidade/epidemiologia , Imunoglobulina E , Inflamação , Microcefalia/epidemiologia , Prevalência , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia
3.
Med Microbiol Immunol ; 212(4): 279-290, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37285099

RESUMO

Chikungunya disease (CHIKD) is an arbovirose that presents with high morbidity, mainly due to arthralgia. Inflammatory mediators including IL-6, IL-1ß, GM-CSF and others have been implicated in the pathogenesis of CHIKD, whilst type I interferons can be associated with better outcomes. The role of pattern recognition receptors has been studied incompletely. Here, we evaluated the expression of RNA-specific PRRs, their adaptor molecules and downstream cytokines in acute CHIKD patients. Twenty-eight patients were recruited during the 3rd-5th day after the symptoms onset for clinical examination, peripheral blood collection and qRT-PCR analysis of PBMC to compare to the healthy control group (n = 20). We observed common symptoms of acute CHIKD, with fever, arthralgia, headache and myalgia being the most frequent. Compared with uninfected controls, acute CHIKV infection upregulates the expression of the receptors TLR3, RIG-I and MDA5, and also the adaptor molecule TRIF. Regarding cytokine expression, we found an upregulation of IL-6, IL-12, IFN-α, IFN-ß and IFN-γ, which are related directly to the inflammatory or antiviral response. The TLR3-TRIF axis correlated with high expression of IL-6 and IFN-α. Interestingly, greater expression of MDA5, IL-12 and IFN-α was related to lower viral loads in CHIKD acute patients. Together, these findings help to complete the picture of innate immune activation during acute CHIKD, while confirming the induction of strong antiviral responses. Drawing the next steps in the understanding of the immunopathology and virus clearance mechanisms of CHIKD should be of utter importance in the aid of the development of effective treatment to reduce the severity of this debilitating disease.


Assuntos
Febre de Chikungunya , Humanos , Receptor 3 Toll-Like , Interleucina-6 , Leucócitos Mononucleares/metabolismo , Imunidade Inata , Citocinas/metabolismo , Interferon-alfa , Interleucina-12 , Artralgia , Proteínas Adaptadoras de Transporte Vesicular , Antivirais
4.
Med Microbiol Immunol ; 211(5-6): 219-235, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35857104

RESUMO

Microcephalic children due congenital Zika virus syndrome (CZS) present neurological symptoms already well described. However, several other alterations can also be observed. Here, we aimed to evaluate the immune system of microcephaly CZS children. We showed that these patients have enlarged thymus, spleen and cervical lymph nodes, analysed by ultrasound and compared to the reference values for healthy children. In the periphery, they have an increase in eosinophil count and morphological alterations as hypersegmented neutrophils and atypical lymphocytes, even in the absence of urinary tract infections, parasitological infections or other current symptomatic infections. Microcephalic children due CZS also have high levels of IFN-γ, IL-2, IL-4, IL-5 and type I IFNs, compared to healthy controls. In addition, this population showed a deficient cellular immune memory as demonstrated by the low reactivity to the tuberculin skin test even though they had been vaccinated with BCG less than 2 years before the challenge with the PPD. Together, our data demonstrate for the first time that CZS can cause alterations in primary and secondary lymphoid organs and also alters the morphology and functionality of the immune system cells, which broadens the spectrum of CZS symptoms. This knowledge may assist the development of specific therapeutic and more efficient vaccination schemes for this population of patients.


Assuntos
Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Criança , Gravidez , Feminino , Humanos , Microcefalia/diagnóstico , Microcefalia/etiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Brasil/epidemiologia
5.
J Med Virol ; 94(10): 4599-4610, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35655326

RESUMO

Historically, passive immunotherapy is an approved approach for protecting and treating humans against various diseases when other alternative therapeutic options are unavailable. Human polyclonal antibodies (hpAbs) can be made from convalescent human donor serum, although it is considered limited due to pandemics and the urgent requirement. Additionally, polyclonal antibodies (pAbs) could be generated from animals, but they may cause severe immunoreactivity and, once "humanized," may have lower neutralization efficiency. Transchromosomic bovines (TcBs) have been developed to address these concerns by creating robust neutralizing hpAbs, which are useful in preventing and/or curing human infections in response to hyperimmunization with vaccines holding adjuvants and/or immune stimulators over an extensive period. Unlike other animal-derived pAbs, potent hpAbs could be promptly produced from TcB in large amounts to assist against an outbreak scenario. Some of these highly efficacious TcB-derived antibodies have already neutralized and blocked diseases in clinical studies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB-185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovine-derived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARS-CoV-2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed.


Assuntos
COVID-19 , HIV-1 , Doença pelo Vírus Ebola , Vírus da Influenza A , Coronavírus da Síndrome Respiratória do Oriente Médio , Infecção por Zika virus , Zika virus , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/uso terapêutico , Anticorpos Amplamente Neutralizantes , COVID-19/terapia , Humanos , Imunoglobulina G , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
6.
Parasit Vectors ; 14(1): 456, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488865

RESUMO

BACKGROUND: Triatomines are responsible for the vector transmission of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Triatoma brasiliensis is the main vector of the parasite in Brazil, and dogs are an important reservoir of the parasite. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on T. brasiliensis after a blood meal in treated dogs. METHODS: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center (ZCC) in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups, a fluralaner (Bravecto®)-treated group (n = 4) and a control group (n = 4). Colony-reared third-, fourth- and fifth-instar nymphs of T. brasiliensis nymphs (n = 10) were allowed to feed on dogs from both groups for 30-40 min, once monthly, for up to 12 months. Bug mortality was observed up to 5 days after each blood meal. RESULTS: Mortality in triatomines which had a blood meal on fluralaner (Bravecto®)-treated dogs was 100% for up to 7 months after treatment, with mortality decreasing to 66.4% after 8 months, 57% after 9 months, 35% after 10 months, 10% after 11 months and 0% after 12 months. The mortality of triatomines that fed on non-treated control dogs was always ≤ 2.5%. CONCLUSIONS: Our results suggest that fluralaner (Bravecto®) treatment of dogs induces long-term mortality of T. brasiliensis after the blood meal. This is a potential approach to be used to control vector transmission of T. cruzi, the etiological agent of Chagas disease, especially in endemic areas.


Assuntos
Doenças do Cão/prevenção & controle , Insetos Vetores/efeitos dos fármacos , Inseticidas/administração & dosagem , Isoxazóis/administração & dosagem , Triatoma/efeitos dos fármacos , Animais , Brasil/epidemiologia , Doença de Chagas/prevenção & controle , Doença de Chagas/transmissão , Doenças do Cão/parasitologia , Cães , Feminino , Insetos Vetores/parasitologia , Masculino , Ninfa/efeitos dos fármacos , Distribuição Aleatória , Triatoma/parasitologia
7.
Front Cell Infect Microbiol ; 11: 696719, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336720

RESUMO

Resistance or susceptibility to T. cruzi infection is dependent on the host immunological profile. Innate immune receptors, such as Toll-like receptors (TLRs/TLR2, TLR4, TLR7, and TLR9) and Nod-like receptors (NLRs/NOD1 and NLRP3 inflammasome) are involved with the resistance against acute experimental T. cruzi infection. Here, we evaluated the impact of T. cruzi virulence on the expression of innate immune receptors and its products in mice. For that, we used six T. cruzi strains/isolates that showed low (AM64/TcIV and 3253/Tc-V), medium (PL1.10.14/TcIII and CL/TcVI), or high (Colombian/Tc-I and Y/TcII) virulence and pathogenicity to the vertebrate host and belonging to the six discrete typing units (DTUs)-TcI to TcVI. Parasitemia, mortality, and myocarditis were evaluated and correlated to the expression of TLRs, NLRs, adapter molecules, cytokines, and iNOS in myocardium by real time PCR. Cytokines (IL-1ß, IL-12, TNF-α, and IFN-γ) were quantified in sera 15 days after infection. Our data indicate that high virulent strains of T. cruzi, which generate high parasitemia, severe myocarditis, and 100% mortality in infected mice, inhibit the expression of TLR2, TLR4, TLR9, TRIF, and Myd88 transcripts, leading to a low IL-12 production, when compared to medium and low virulent T. cruzi strains. On the other hand, the high virulent T. cruzi strains induce the upregulation of NLRP3, caspase-1, IL-1ß, TNF-α, and iNOS mRNA in heart muscle, compared to low and medium virulent strains, which may contribute to myocarditis and death. Moreover, high virulent strains induce higher levels of IL-1ß and TNF-α in sera compared to less virulent parasites. Altogether the data indicate that differential TLR and NLR expression in heart muscle is correlated with virulence and pathogenicity of T cruzi strains. A better knowledge of the immunological mechanisms involved in resistance to T. cruzi infection is important to understand the natural history of Chagas disease, can lead to identification of immunological markers and/or to serve as a basis for alternative therapies.


Assuntos
Doença de Chagas , Imunidade Inata , Miocárdio/imunologia , Trypanosoma cruzi , Animais , Caspase 1 , Coração , Camundongos , Trypanosoma cruzi/patogenicidade , Virulência
8.
Parasit Vectors ; 13(1): 609, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276818

RESUMO

BACKGROUND: Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in the New World, where the sand fly Lutzomyia longipalpis and domestic dogs are considered the main vector and host reservoirs, respectively. Systemic insecticides have been studied as an alternative to control vector-borne diseases, including VL. Fluralaner, an isoxazoline class compound, is a systemic insecticide used in dogs, with proven efficiency against different species of phlebotomine sand flies. However, to date no studies have demonstrated the efficacy of fluralaner on Lu. longipalpis. The aim of this study was to evaluate the insecticidal effect of fluralaner (Bravecto®) on the sand fly Lu. longipalpis after blood meal in treated dogs. METHODS: Healthy mongrel dogs (n = 8) were recruited from the Zoonoses Control Center in the city of Natal, Rio Grande do Norte, Brazil, and randomized into two groups: fluralaner treated (n = 4) and non-treated control (n = 4). Colony-reared female specimens of Lu. longipalpis (n = 20) were allowed to feed on all dogs for 40 min before treatment (for fluralaner-treated dogs), at day 1 after treatment and then monthly until 1 year post-treatment. RESULTS: In the treatment group, there was 100% mortality of Lu. longipalpis for up to 5 months after treatment initiation, decreasing to 72.5% at 6 months post-treatment initiation. The efficacy of fluralaner ranged from 100% at day 1 (P = 0.0002) to 68% ( P = 0.0015) at 6 months, decreasing to 1.4% at 1 year post-treatment. Sand fly mortality carried out blood meal in non-treated control dogs remained constant at ≤ 15%. CONCLUSIONS: Taken together, our results suggest that fluralaner may be used as a control strategy for VL in dogs in VL endemic areas.


Assuntos
Doenças do Cão , Inseticidas , Isoxazóis , Refeições , Psychodidae , Animais , Cães , Feminino , Masculino , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Insetos Vetores , Inseticidas/farmacologia , Isoxazóis/farmacologia , Leishmania infantum , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Psychodidae/efeitos dos fármacos , Psychodidae/parasitologia
9.
PLoS Negl Trop Dis ; 14(9): e0008667, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32986710

RESUMO

Digestive and cardiodigestive forms of Chagas' disease are observed in 2% to 27% of the patients, depending on their geographic location, Trypanosoma cruzi strain and immunopathological responses. The aim of this work was to evaluate the role of NOD2 innate immune receptor in the pathogenesis of the digestive system in Chagas' disease. Patients with digestive form of the disease showed lower mRNA expression of NOD2, higher expression of RIP2 and α-defensin 6, compared to indeterminate form, detected by Real-time PCR in peripheral blood mononuclear cells. In addition, there was a negative correlation between the expression of NOD2 and the degree of dilation of the esophagus, sigmoid and rectum in those patients. The infection of NOD2-/- mice with T. cruzi strain isolated from the digestive patient induced a decrease in intestinal motility. Histopathological analysis of the colon and jejunum of NOD2-/- and wild type C57BL/6 animals revealed discrete inflammatory foci during the acute phase of infection. Interestingly, during the chronic phase of the infection there was inflammation and hypertrophy of the longitudinal and circular muscular layer more pronounced in the colon and jejunum from NOD2-/- animals, when compared to wild type C57BL/6 mice. Together, our results suggest that NOD2 plays a protective role against the development of digestive form of Chagas' disease.


Assuntos
Doença de Chagas/imunologia , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/imunologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Trypanosoma cruzi/imunologia , Adolescente , Adulto , Idoso , Animais , Brasil , Doença de Chagas/patologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Adulto Jovem , alfa-Defensinas/genética , alfa-Defensinas/metabolismo
10.
J Vis Exp ; (151)2019 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-31609344

RESUMO

Marmosets (Callithrix jacchus) are small non-human primates that are gaining popularity in biomedical and preclinical research, including the neurosciences. Phylogenetically, these animals are much closer to humans than rodents. They also display complex behaviors, including a wide range of vocalizations and social interactions. Here, an effective stereotaxic neurosurgical procedure for implantation of recording electrode arrays in the common marmoset is described. This protocol also details the pre- and postoperative steps of animal care that are required to successfully perform such a surgery. Finally, this protocol shows an example of local field potential and spike activity recordings in a freely behaving marmoset 1 week after the surgical procedure. Overall, this method provides an opportunity to study the brain function in awake and freely behaving marmosets. The same protocol can be readily used by researchers working with other small primates. In addition, it can be easily modified to allow other studies requiring implants, such as stimulating electrodes, microinjections, implantation of optrodes or guide cannulas, or ablation of discrete tissue regions.


Assuntos
Microeletrodos/normas , Procedimentos Neurocirúrgicos/métodos , Animais , Callithrix
11.
Med Microbiol Immunol ; 208(6): 703-714, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30879197

RESUMO

Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-α and IFN-ß production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-ß/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-ß, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-ß, and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-α and IFN-ß. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-α molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-γ, IFN-α, and IFN-ß, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß in ZIKV patients.


Assuntos
Imunidade Inata , Fatores Imunológicos/biossíntese , Receptores Imunológicos/biossíntese , Infecção por Zika virus/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Zika virus/isolamento & purificação
12.
PLoS Negl Trop Dis ; 12(7): e0006589, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30044791

RESUMO

Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-1) and cytokines (IL-1ß, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-ß) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-ß (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-ß mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1ß mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1ß, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1ß and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction.


Assuntos
Cardiomiopatia Chagásica/imunologia , Doenças do Sistema Digestório/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteínas NLR/imunologia , Adulto , Idoso , Caspase 1/genética , Caspase 1/imunologia , Cardiomiopatia Chagásica/genética , Cardiomiopatia Chagásica/parasitologia , Doenças do Sistema Digestório/genética , Doenças do Sistema Digestório/parasitologia , Feminino , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR/genética , Trypanosoma cruzi/fisiologia
13.
Acta Trop ; 172: 1-6, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28427965

RESUMO

T1/ST2 is a surface marker selectively expressed on type 2 helper (TH2) effector cells. As Leishmania infection in susceptible BALB/c mice have ascribed to a polarized TH2 response, this study aim to investigate the T1/ST2 (the receptor for IL-33), as a typical TH2 marker in the postulation that a shift towards a beneficial TH1 response would occur in the absence of ST2. For this, ST2 knockout (ST2-/-) and WT BALB/c mice were experimentally infected in the retro-orbital sinus with L. infantum. We showed that ST2-/- animals displayed better control of parasite burden in both spleen and liver tissues at different time points of chronic phases, and reduced spleenomegaly and hepatomegaly compared with the wild-type (WT) mice. This was associated with increased in the IFN-γ levels and expression by CD4+ and CD8+ lymphocytes. The inflammatory response encompasses transaminases (AST and ALT) releases and NO productions were remarkably lower in ST2-/- mice compared with WT. These data suggest that, ST2-/-) exert protection against L. infantum infection and probably shift the immune response toward TH1 induction.


Assuntos
Interleucina-33/imunologia , Leishmania infantum/crescimento & desenvolvimento , Leishmania infantum/imunologia , Leishmaniose/imunologia , Células Th2/imunologia , Animais , Linfócitos T CD8-Positivos , Feminino , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Baço/imunologia
14.
PLoS Negl Trop Dis ; 10(4): e0004669, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27115869

RESUMO

Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.


Assuntos
Doença de Chagas/complicações , Doença de Chagas/mortalidade , Inflamação/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Adulto , Idoso , Doença de Chagas/patologia , Doença Crônica , Citocinas/biossíntese , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/patologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Medição de Risco , Análise de Sobrevida
15.
J Infect Dis ; 211(6): 1015-26, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25274569

RESUMO

Interleukin 17 (IL-17) is an inflammatory cytokine that plays a protective role against intracellular parasites. The role of IL-17 during Leishmania infection remains controversial and poorly defined. We evaluated whether IL-17 participates in the host immune response to Leishmania infantum. IL-17A is present in sera from patients with visceral leishmaniasis and decreases after successful treatment. In C57BL/6 infected mice, higher production of IL-17A coincided with the peak of parasitism. Il17ra(-/-) mice were more susceptible to infection and also exhibited reduced inflammatory infiltration and interferon γ (IFN-γ)-expressing CD4+ T-cell frequencies than wild-type mice. The frequencies of FoxP3+ CD4+ T cells and interleukin 10 (IL-10)-expressing CD4+ T cells were increased in Il17ra(-/-) mice. We also demonstrated that IL-17A acts synergistically with IFN-γ to potentiate NO production and leishmanicidal activity in infected macrophages. Therefore, our results indicate that L. infantum induces IL-17A production, which promotes the control of parasite replication by strengthening T-helper type 1 responses and NO production and prevents regulatory T-cell and IL-10-expressing T-cell expansion.


Assuntos
Interferon gama/fisiologia , Interleucina-17/fisiologia , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Adolescente , Adulto , Animais , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Celular , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/parasitologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/parasitologia , Adulto Jovem
16.
Rev Bras Parasitol Vet ; 21(2): 151-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22832757

RESUMO

To confirm that Beagle dogs are a good experimental model for Chagas disease, we evaluated hematological alterations during the acute and chronic phases in Beagle dogs infected with the Y, Berenice-78 (Be-78) and ABC strains of Trypanosomacruzi, correlating clinical signs with the parasitemia curve. We demonstrate that the acute phase of infection was marked by lethargy and loss of appetite. Simultaneously, we observed anemia, leukocytosis and lymphocytosis. Also,we describe hematological alterations and clinical signs that were positively correlated with the parasitemia during the experimental infection with the three strains of T.cruzi, and demonstrate that experimental infection of Beagle is a trustworthy model for Chagas disease.


Assuntos
Doença de Chagas/complicações , Modelos Animais de Doenças , Doenças Hematológicas/etiologia , Animais , Cães
17.
Trop Med Int Health ; 17(9): 1057-65, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22686518

RESUMO

Chronic chagasic cardiomyopathy affects 20% of Chagas' disease patients. At present, Chagas' disease chemotherapy uses nitrofurans, benznidazole (Rochagan®, Rodanil®, Roche) or nifurtimox (Lampit®, Bayer). Treatment during acute and recent chronic phases in childhood effects 71.5% and 57.6%, respectively, of parasitological cure. However, in clinical trials during the late chronic phase, only 5.9% of parasitological cure were achieved. This review focuses on the benefit from aetiological treatment to avoid, stop or revert myocarditis. Divergent data gathered from clinical practice are not convincing to support prescription of aetiological treatment as routine for indeterminate and cardiac chronic patients.


Assuntos
Antiparasitários/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Trypanosoma cruzi , Doença Aguda , Antiparasitários/administração & dosagem , Antiparasitários/efeitos adversos , Doença Crônica , Ensaios Clínicos como Assunto , Humanos
18.
Rev. Bras. Parasitol. Vet. (Online) ; 21(2): 151-156, abr.-jun. 2012.
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1487793

RESUMO

To confirm that Beagle dogs are a good experimental model for Chagas disease, we evaluated hematological alterations during the acute and chronic phases in Beagle dogs infected with the Y, Berenice-78 (Be-78) and ABC strains of Trypanosoma cruzi, correlating clinical signs with the parasitemia curve. We demonstrate that the acute phase of infection was marked by lethargy and loss of appetite. Simultaneously, we observed anemia, leukocytosis and lymphocytosis. Also,we describe hematological alterations and clinical signs that were positively correlated with the parasitemia during the experimental infection with the three strains of T.cruzi, and demonstrate that experimental infection of Beagle is a trustworthy model for Chagas disease.


Para confirmar que cães Beagle são um bom modelo para doença de Chagas, foram avaliadas as alterações hematológicas durante as fases aguda e crônica em cães Beagle infectados com as cepas Y, Berenice-78 (Be-78) e ABC de Trypanosomacruzi, correlacionando os sinais clínicos com a curva de parasitemia. Foi demonstrado que a fase aguda da infecção foi marcada por letargia e perda de apetite. Simultaneamente, observou-se anemia, leucocitose e linfocitose. Ainda, foram descritas alterações hematológicas e sinais clínicos positivamente correlacionados com a parasitemia durante a infecção experimental com as três cepas de T.cruzi estudadas, demonstrando que a infecção em cães Beagle constitui um modelo fidedigno para a doença de Chagas.


Assuntos
Animais , Cães , Anemia , Doença de Chagas , Leucocitose , Linfocitose , Parasitemia , Trypanosoma cruzi/parasitologia , Trypanosoma cruzi/patogenicidade , Modelos Animais de Doenças
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