Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.442
Filtrar
1.
Exp Parasitol ; 221: 108059, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338468

RESUMO

Treatment for visceral leishmaniasis (VL) is hindered mainly by the toxicity and/or high cost of therapeutic drugs. In addition, parasite resistance has been registered. Thus, there is an urgent need for the identification of novel, effective and low-cost antileishmanial agents. Since drug discovery is a long and expensive process, drug repositioning for treatment of leishmaniasis should be considered. In the present study, Ivermectin (IVE), a broad-spectrum drug used for treatment of parasitic diseases, was evaluated in vitro and in vivo against Leishmania infantum species. Results in vitro showed that IVE presented 50% Leishmania and macrophage inhibitory concentrations (IC50 and CC50, respectively) of 3.64 ± 0.48 µM and 427.50 ± 17.60 µM, respectively, with a selectivity index (SI) of 117.45; whereas Amphotericin B (AmpB), which was used as control, showed IC50 and CC50 values of 0.12 ± 0.05 µM and 1.06 ± 0.23 µM, respectively, with a corresponding SI of 8.90. Treatment with IVE effectively reduced the infection percentage and parasite burden in infected and treated macrophages and displayed a prophylactic activity by inhibiting macrophage infection with pre-treated parasites. Furthermore, preliminary studies suggested that IVE targets the parasite's mitochondria. Activity of IVE in its free format or incorporated into Pluronic® F127-based polymeric micelles (IVE/Mic) was also evaluated in vivo as a treating drug for L. infantum-infected BALB/c mice. Miltefosine was used as a control. Results showed that Miltefosine, IVE and IVE/Mic-treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as well as development of an antileishmanial Th1-type immune response one and 15 days after treatment. Notably, IVE/Mic showed a better parasitological and immunological response in comparison to other alternative treatments. In conclusion, results suggest that IVE/Mic could be considered in future studies as a therapeutic alternative to treat VL.


Assuntos
Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/farmacologia , Animais , Antiprotozoários/toxicidade , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Concentração Inibidora 50 , Ivermectina/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Baço/parasitologia
2.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(6): 591-597, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33325193

RESUMO

OBJECTIVE: To examine the changes in the immune functions of CD8+ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. METHODS: The E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8+ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. RESULTS: A central-memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8+ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8+ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8+ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8+ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8+ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8+ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8+ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). CONCLUSIONS: E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8+ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Equinococose/imunologia , Baço/imunologia , Animais , Citocinas/imunologia , Echinococcus multilocularis , Camundongos , Baço/parasitologia
3.
PLoS Negl Trop Dis ; 14(12): e0009015, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370305

RESUMO

Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host's skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host's bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates.


Assuntos
Doença de Chagas/transmissão , Linfonodos/parasitologia , Pele/parasitologia , Baço/parasitologia , Trypanosoma rangeli/isolamento & purificação , Animais , América Central/epidemiologia , Doença de Chagas/epidemiologia , Modelos Animais de Doenças , Interações Hospedeiro-Parasita , Humanos , Mordeduras e Picadas de Insetos/parasitologia , Insetos Vetores/parasitologia , Camundongos , Rhodnius/parasitologia , Sepse/parasitologia , América do Sul/epidemiologia
4.
Parasitol Res ; 119(9): 3041-3051, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32779021

RESUMO

Our objective was to investigate clinical progression, presence of parasites and DNAs, parasite loads, and histological alterations in BALB/c mice and Syrian golden hamsters after intraperitoneal inoculation with Leishmania (Mundinia) martiniquensis promastigotes with a goal to choosing an appropriate animal model for visceral leishmaniasis. Infections were monitored for 16 weeks. Infected BALB/c mice were asymptomatic during the infection course. Parasite DNAs were detected in the liver at week 8 of infection, followed by clearance in most animals at week 16; whereas in the spleen, parasite DNAs were detected until week 16. These results are correlated to those obtained measuring parasite loads in both organs. No parasite DNA and no alteration in the bone marrow were observed indicating that no dissemination occurred. These results suggest the control of visceralization of L. martiniquensis by BALB/c mice. In hamsters, weight loss, cachexia, and fatigue were observed after week 11. Leishmania martiniquensis parasites were observed in tissue smears of the liver, spleen, and bone marrow by week 16. Parasite loads correlated with those from the presence of parasites and DNAs in the examined tissues. Alterations in the liver with nuclear destruction and cytoplasmic degeneration of infected hepatocytes, presence of inflammatory infiltrates, necrosis of hepatocytes, and changes in splenic architecture and reduction and deformation of white pulp in the spleen were noted. These results indicate a chronic form of visceral leishmaniasis indicating that the hamster is a suitable animal model for the study of pathological features of chronic visceral leishmaniasis caused by L. martiniquensis.


Assuntos
Leishmania/fisiologia , Leishmaniose Visceral/parasitologia , Animais , Cricetinae , Modelos Animais de Doenças , Humanos , Leishmania/genética , Fígado/parasitologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Baço/parasitologia
5.
Exp Parasitol ; 217: 107966, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32781094

RESUMO

Toxoplasma gondii has long been considered a ubiquitous parasite possessing the capacity of infecting virtually all warm-blooded animals globally. Occasionally, this parasite can also infect cold-blooded animals such as fish if their body temperature reaches 37 °C. However, we are currently lacking an understanding of key details such as the minimum temperature required for T. gondii invasion and proliferation in these cold-blooded animals and their cells. Here, we performed in vitro T. gondii infection experiments with rat embryo fibroblasts (REF cells), grouper (Epinephelus coioides) splenocytes (GS cells) and zebra fish (Danio rerio) hepatocytes (ZFL cells), at 27 °C, 30 °C, 32 °C, 35 °C and 37 °C, respectively. We found that T. gondii tachyzoites could penetrate REF, GS nd ZFL cells at 27 °C but clear inhibition of multiplication was observed. Intriguingly, the intracellular tachyzoites retained the ability to infect mice after 12 days of incubation in GS cells cultured at 27 °C as demonstrated by bioassay. At 30 °C, 32 °C and 35 °C, we observed that the mammalian cells (REF cells) and fish cells (GS and ZFL cells) could support T. gondii invasion and replication, which showed a temperature-dependent relationship in infection and proliferation rates. Our data demonstrated that the minimum temperature for T. gondii invasion and replication was 27 °C and 30 °C respectively, which indicated that temperature should be a key factor for T. gondii invasion and proliferation in host cells. This suggests that temperature-dependent infection determines the differences in the capability of T. gondii to infect cold- and warm-blooded vertebrates.


Assuntos
Bass/parasitologia , Fibroblastos/parasitologia , Hepatócitos/parasitologia , Temperatura , Toxoplasma/fisiologia , Peixe-Zebra/parasitologia , Animais , Bioensaio , Temperatura Corporal , Feminino , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Baço/citologia , Baço/parasitologia , Toxoplasma/crescimento & desenvolvimento
6.
Exp Parasitol ; 216: 107941, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32622940

RESUMO

Distinct antigens have been evaluated with diagnostic purpose for canine and human visceral leishmaniasis (VL), and variable sensitivity and specificity values have been obtained in the assays. In the present study, a Leishmania infantum hypothetical protein called LiHyG, which was identified in an immunoproteomics study in Leishmania infantum amastigote extracts by antibodies in VL dogs sera; was cloned, expressed, purified and evaluated as a recombinant protein (rLiHyG) for the diagnosis of canine and human disease. The recombinant amastigote-specific A2 protein (rA2) and a soluble L. infantum protein extract (SLA) were used as controls. For canine VL, the sensitivity values were of 100%, 57.29% and 48.57%, when rLiHyG, rA2 and SLA were used, respectively, while the specificity values were of 100%, 81.43% and 88.57%, respectively. In addition, AUC values were of 1.00, 0.72 and 0.65, when rLiHyG, rA2 and SLA were used, respectively, while accuracy was of 100%, 72.38% and 75.24%, respectively. For human VL, the sensitivity values were of 100%, 84.00% and 88.00%, when rLiHyG, rA2 and SLA were used, respectively, while the specificity values were of 100%, 58.75% and 73.75%, respectively. In addition, AUC values were of 1.00, 0.76 and 0.83, when rLiHyG, rA2 and SLA were used, respectively, while accuracy was of 100%, 64.8% and 66.6%, respectively. The prognostic role of rLiHyG in the human VL was also evaluated, by means of post-therapeutic serological follow-up with sera samples collected before and six months after treatment. Results showed that treated patients presented significant reductions in the anti-rLiHyG IgG, IgG1, and IgG2 antibody levels, with results being similar to those found in healthy subjects. Testing the rA2 protein and SLA as antigens, lower IgG, IgG1, and IgG2 levels were also found, although they were higher after treatment than those obtained for rLiHyG. In conclusion, results suggested that rLiHyG could be considered for future studies as a diagnostic and/or prognostic marker for canine and human VL.


Assuntos
Antígenos de Protozoários/isolamento & purificação , Doenças do Cão/parasitologia , Leishmania infantum/imunologia , Leishmaniose Visceral/diagnóstico , Adulto , Idoso , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/genética , Medula Óssea/parasitologia , Biologia Computacional , DNA de Protozoário/química , DNA de Protozoário/isolamento & purificação , Doenças do Cão/diagnóstico , Cães , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito B/química , Feminino , Humanos , Imunoglobulina G/sangue , Leishmania infantum/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Protozoários/química , Sensibilidade e Especificidade , Alinhamento de Sequência , Testes Sorológicos , Baço/parasitologia , Adulto Jovem
7.
Exp Parasitol ; 216: 107946, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32622941

RESUMO

This study was aimed at investigating the involvement of Receptor for Advanced Glycation End Products (RAGE) during malaria infection and the effects of modulating RAGE on the inflammatory cytokines release and histopathological conditions of affected organs in malarial animal model. Plasmodium berghei (P. berghei) ANKA-infected ICR mice were treated with mRAGE/pAb and rmRAGE/Fc Chimera drugs from day 1 to day 4 post infection. Survival and parasitaemia levels were monitored daily. On day 5 post infection, mice were sacrificed, blood were drawn for cytokines analysis and major organs including kidney, spleen, liver, brain and lungs were extracted for histopathological analysis. RAGE levels were increased systemically during malaria infection. Positive correlation between RAGE plasma concentration and parasitaemia development was observed. Treatment with RAGE related drugs did not improve survival of malaria-infected mice. However, significant reduction on the parasitaemia levels were recorded. On the other hand, inhibition and neutralization of RAGE production during the infection significantly increased the plasma levels of interleukin (IL-4, IL-17A, IL-10 and IL-2) and reduced interferon (IFN)-γ secretion. Histopathological analysis revealed that all treated malarial mice showed a better outcome in histological assessment of affected organs (brain, liver, spleen, lungs and kidney). RAGE is involved in malaria pathogenesis and targeting RAGE could be beneficial in malaria infected host in which RAGE inhibition or neutralization increased the release of anti-inflammatory cytokines (IL-10 and IL-4) and reduce pro-inflammatory cytokine (IFNγ) which may help alleviate tissue injury and improve histopathological conditions of affected organs during the infection.


Assuntos
Citocinas/metabolismo , Malária/imunologia , Malária/patologia , Plasmodium berghei/imunologia , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Citocinas/sangue , Rim/parasitologia , Rim/patologia , Modelos Lineares , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Parasitemia/imunologia , Distribuição Aleatória , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/imunologia , Baço/parasitologia , Baço/patologia
8.
Trends Parasitol ; 36(9): 721-723, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32507384

RESUMO

Occasionally, Plasmodium falciparum malaria is apparently precipitated by traumatic events (e.g., a landmine accident) or by noninfectious events (e.g., pregnancy). The authors reporting such cases often seem as baffled as many of their readers probably are. However, the case reports may contain important clues regarding malaria pathogenesis and immunity.


Assuntos
Malária , Humanos , Malária/complicações , Malária/imunologia , Malária/parasitologia , Malária/transmissão , Plasmodium falciparum/imunologia , Plasmodium falciparum/patogenicidade , Baço/parasitologia , Esplenopatias/etiologia , Esplenopatias/parasitologia , Ferimentos e Lesões/complicações
9.
Exp Parasitol ; 215: 107933, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32525006

RESUMO

Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.


Assuntos
Piridinas/farmacologia , Quinolinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/farmacologia , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Feminino , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Óxido Nítrico/análise , Piridinas/química , Piridinas/uso terapêutico , Quinolinas/química , Quinolinas/uso terapêutico , Distribuição Aleatória , Esquistossomicidas/química , Esquistossomicidas/uso terapêutico , Fatores Sexuais , Baço/parasitologia , Baço/patologia
10.
Ann Parasitol ; 66(2): 251-254, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32592548

RESUMO

Ouagadougou, the capital city of Burkina Faso, was recognized as a focus of zoonotic cutaneous leishmaniosis in April 2000. Leishmania major was the only strain isolated in this focus. We conducted a prospective study to detect L. major in rodents, animals which are described as reservoir of the parasite. Rodents were caught in five city areas from November 2005 to October 2006. Giemsa stained smears were realized from the cutaneous lesions when present after macroscopic examination of external lesions. The spleen of each rodent was sterilely removed and split into 3 parts for microscopic examination of smears, culture on NNN media and PCR, respectively. A total of 101 rodents belonging to 9 genera were trapped. All the direct examinations and cultures were negative. By using PCR of lesions and spleen samples, three animals were found infected by L. major: one out of 24 (4.2%) Mastomys natalensis; one out of 8 (12.5%) Taterillus sp. and one out of three Cricetomys gambianus. This is the first detection of L. major in rodent species in Burkina Faso. Further studies are needed to confirm their role as reservoirs of L. major.


Assuntos
Reservatórios de Doenças , Leishmania major , Leishmaniose Cutânea , Reação em Cadeia da Polimerase , Doenças dos Roedores , Roedores , Animais , Burkina Faso , Reservatórios de Doenças/parasitologia , Leishmania major/genética , Leishmaniose Cutânea/diagnóstico , Estudos Prospectivos , Doenças dos Roedores/parasitologia , Roedores/parasitologia , Baço/parasitologia
11.
J Med Chem ; 63(11): 5734-5751, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392053

RESUMO

Leishmania (L.) infantum causes visceral, cutaneous, and mucosal leishmaniasis in humans and canine leishmaniasis in dogs. Herein, we describe that O-alkyl hydroxamate derivatives displayed potent and selective in vitro activity against the amastigote stage of L. infantum while no activity was observed against promastigotes. Compound 5 showed potent in vivo activity against L. infantum. Moreover, the combination of compound 5 supported on gold nanoparticles and meglumine antimoniate was also effective in vivo and improved the activity of these compounds compared to that of the individual treatment. Docking studies showed that compound 5 did not reach highly conserved pocket C and established interactions with the semiconserved residues V44, A45, R242, and E243 in pocket A of LiSIR2rp1. The surface space determined by these four amino acids is not conserved in human sirtuins. Compound 5 represents a new class of selective ligands with antileishmanial activity.


Assuntos
Antiprotozoários/farmacologia , Ácidos Hidroxâmicos/química , Leishmania infantum/efeitos dos fármacos , Animais , Antiprotozoários/química , Sítios de Ligação , Feminino , Ouro/química , Histona Desacetilase 1/química , Histona Desacetilase 1/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Leishmania infantum/crescimento & desenvolvimento , Estágios do Ciclo de Vida/efeitos dos fármacos , Antimoniato de Meglumina/farmacologia , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Microssomos Hepáticos/metabolismo , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Baço/parasitologia
12.
Proc Natl Acad Sci U S A ; 117(23): 13056-13065, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32439708

RESUMO

Plasmodium vivax, the most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in Plasmodium knowlesi, another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression. Hence, using a global transcriptional analysis of parasites obtained from spleen-intact and splenectomized monkeys, we identified 67 P. vivax genes whose expression was spleen dependent. To determine their role in cytoadherence, two Plasmodium falciparum transgenic lines expressing two variant proteins pertaining to VIR and Pv-FAM-D multigene families were used. Cytoadherence assays demonstrated specific binding to human spleen but not lung fibroblasts of the transgenic line expressing the VIR14 protein. To gain more insights, we expressed five P. vivax spleen-dependent genes as recombinant proteins, including members of three different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one membrane transporter (SECY), and one hypothetical protein (HYP1), and determined their immunogenicity and association with clinical protection in a prospective study of 383 children in Papua New Guinea. Results demonstrated that spleen-dependent antigens are immunogenic in natural infections and that antibodies to HYP1 are associated with clinical protection. These results suggest that the spleen plays a major role in expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus prompting a paradigm shift in P. vivax biology toward deeper studies of the spleen during infections.


Assuntos
Antígenos de Protozoários/imunologia , Genes de Protozoários , Malária Vivax/imunologia , Plasmodium vivax/imunologia , Baço/metabolismo , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos de Protozoários/genética , Aotidae , Células CHO , Adesão Celular/genética , Adesão Celular/imunologia , Criança , Cricetulus , Modelos Animais de Doenças , Fibroblastos , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Malária Vivax/sangue , Malária Vivax/parasitologia , Família Multigênica , Papua Nova Guiné , Plasmodium vivax/genética , Baço/citologia , Baço/parasitologia , Esplenectomia , Análise Serial de Tecidos
13.
Trends Parasitol ; 36(5): 435-446, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32298631

RESUMO

The human spleen is an immune sentinel and controls red blood cell (RBC) quality. By mechanically retaining subsets of infected RBCs, the spleen may reduce the pace at which the parasite biomass increases before the adaptive immune response operates. Conversely, the spleen may contribute to malaria pathogenesis, particularly anemia that is associated with splenomegaly. Large spleens may also shelter parasites in chronic carriers. Upon treatment with artemisinins, the spleen clears circulating parasites by pitting and releases 'once-infected' RBCs in circulation. This triggers postartesunate delayed hemolysis and explains the long post-treatment positivity of histidine-rich protein 2 (HRP2)-based dipsticks. Importantly, splenic retention of RBCs also applies to gametocytes, the clearance of which may be enhanced by stiffening them with drugs, a potential way to block malaria transmission.


Assuntos
Malária Falciparum/parasitologia , Baço/parasitologia , Eritrócitos/imunologia , Eritrócitos/parasitologia , Humanos , Malária Falciparum/imunologia , Plasmodium falciparum/fisiologia , Baço/imunologia
14.
Zool Res ; 41(3): 314-327, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32242645

RESUMO

Host-pathogen interactions are highly complex, involving large dynamic changes in gene expression during infection. These interactions are fundamental to understanding anti-infection immunity of hosts, as well as the pathogenesis of pathogens. For bacterial pathogens interacting with animal hosts, time-resolved dual RNA-seq of infected tissue is difficult to perform due to low pathogen load in infected tissue. In this study, an acute infection model of Larimichthys crocea infected by Pseudomonas plecoglossicida was established. The spleens of infected fish exhibited typical symptoms, with a maximum bacterial load at two days post-injection (dpi). Time-resolved dual RNA-seq of infected spleens was successfully applied to study host-pathogen interactions between L. crocea and P. plecoglossicida. The spleens of infected L. crocea were subjected to dual RNA-seq, and transcriptome data were compared with those of noninfected spleens or in vitro cultured bacteria. Results showed that pathogen-host interactions were highly dynamically regulated, with corresponding fluctuations in host and pathogen transcriptomes during infection. The expression levels of many immunogenes involved in cytokine-cytokine receptor, Toll-like receptor signaling, and other immune-related pathways were significantly up-regulated during the infection period. Furthermore, metabolic processes and the use of oxygen in L. crocea were strongly affected by P. plecoglossicida infection. The WGCNA results showed that the metabolic process was strongly related to the entire immune process. For P. plecoglossicida, the expression levels of motility-related genes and flagellum assembly-related genes were significantly up-regulated. The results of this study may help to elucidate the interactions between L. crocea and P. plecoglossicida.


Assuntos
Doenças dos Peixes/parasitologia , Perciformes , Infecções por Pseudomonas/veterinária , Pseudomonas/isolamento & purificação , Animais , Proteínas de Bactérias/análise , Interações Hospedeiro-Patógeno , Infecções por Pseudomonas/parasitologia , RNA-Seq/veterinária , Baço/parasitologia
15.
Parasitol Res ; 119(5): 1683-1690, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32285265

RESUMO

The diagnosis of canine visceral leishmaniasis (CVL) has been a problem for public health services due to the variety of clinical signs similar to other diseases and low sensitivity and specificity of available tests. In this sense, our main objective was to develop a simple, rapid, and accurate quantitative real-time PCR (qPCR) diagnosis for CVL. Thus, low-invasive samples from bone marrow (BM), popliteal lymph nodes (PLN), and conjunctival swabs (CS) were selected from negative and VL-positive dogs, using as gold standard, immunological and parasitological tests performed with different tissues. Oligonucleotides for Leishmania infantum kDNA were designed and the limit of quantification and amplification efficiency of the qPCR were determined using tissue-specific standards produced with DNA from those different tissues, mixed with DNA from a known amount of L. infantum promastigotes. Endogenous control was used to validate a comparative Ct method, and tissue parasite concentrations were estimated by comparison with tissue-specific reference standard samples. The overall analysis of the qPCR data suggests the following ranking for tissue choice: PLN > BM > CS. Finally, we have concluded that this molecular approach simplifies and accelerates the quantitative diagnostic process because it is easy to perform, requiring no DNA dosing or standard curve application, and it shows good diagnostic parameters, especially when using popliteal lymph node samples.


Assuntos
Doenças do Cão/diagnóstico , Leishmania infantum/genética , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Medula Óssea/parasitologia , DNA de Cinetoplasto/genética , Doenças do Cão/parasitologia , Cães , Leishmaniose Visceral/parasitologia , Linfonodos/parasitologia , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sensibilidade e Especificidade , Baço/parasitologia
16.
Poult Sci ; 99(3): 1326-1331, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115023

RESUMO

IL-6, IL-8, and C-C motif chemokine ligand 2 (CCLi2) are important factors in inflammatory and immune responses. To investigate their relationships in the spleen and cecum and between coccidiosis-infected and uninfected states, we performed quantitative real-time PCR to compare the relative expression difference of IL-6, IL-8, and CCLi2 in the same tissues between the infection and control groups. In addition, the correlations of the relative expression levels of these 3 genes were determined in the same and different tissues within the same group. The results showed that the expression levels of IL-6, IL-8, and CCLi2 in the spleen and cecum of the infected group were all higher than those of the uninfected group (P < 0.05). The correlation coefficients among the IL-6, IL-8, and CCLi2 expression levels in the spleen or cecum were all positive in both the infection and control groups. In the spleen tissues, CCLi2 expression was strongly correlated with IL-6 and IL-8 in the uninfected group (P < 0.01), and the correlation coefficients reached 0.853 (R2 = 0.728) and 0.996 (R2 = 0.992), respectively. The expression of CCLi2 was also strongly correlated with IL-8 (R reached 0.890, R2 = 0.792) in the infected group. In the cecal tissues, the expression levels of the 3 genes were all extremely significantly correlated in the uninfected group (P < 0.01), and the correlation coefficients ranged from 0.498 to 0.765, indicating moderate correlations. The expression of IL-6 was extremely significantly positively correlated with IL-8 and CCLi2 in the infected group (P < 0.01), with moderate correlations (R ranged from 0.469-0.639). In addition, the expression levels of the 3 genes were not significantly correlated (P > 0.05) between the spleen and cecum tissues in either the infection group or the control group. These results indicate that IL-6, IL-8, and CCLi2 were correlated and play an important role in coccidiosis infection of Jinghai yellow chicken. Our data also provide a basis for further exploring the role of these 3 genes in genetic breeding for coccidiosis resistance.


Assuntos
Proteínas Aviárias/genética , Coccidiose/veterinária , Eimeria tenella/fisiologia , Expressão Gênica , Doenças das Aves Domésticas/genética , Animais , Proteínas Aviárias/metabolismo , Ceco/metabolismo , Ceco/parasitologia , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Coccidiose/genética , Coccidiose/parasitologia , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Ligantes , Doenças das Aves Domésticas/parasitologia , Baço/metabolismo , Baço/parasitologia
17.
PLoS One ; 15(3): e0230381, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176727

RESUMO

Visceral leishmaniasis (VL) is the most fatal form of leishmaniasis if left untreated and 50,000 to 90,000 new cases of VL occur worldwide each year. Although various vaccines had been studied in animal models, none of them was eligible to prevent human from infections. In this study, according to the silico analysis of Leishmania Amastin, Kmp-11 and Gp63 protein, dominant epitope sequences of these proteins were selected and linked to construct dominant multi-epitopes DNA and protein vaccines (Amastin-Kmp-11, Amastin-Gp63 and Kmp-11-Gp63) against VL. BALB/c mice were immunized with a DNA prime-protein boost immunization strategy and challenged with a new Leishmania parasite strain isolated from a VL patient. After immunization, the results including specific antibody titers, IL-4 and TNF-α levels, and CD4 and CD8 T cell proportion suggested the potent immunogenicity of the three vaccines. After infection, the results of spleen parasite burdens in the three vaccine groups were significantly lower than those of control groups, and the parasite reduction rates of Amastin-Kmp-11, Amastin-Gp63 and Kmp-11-Gp63 groups were 89.38%, 91.01% and 88.42%, respectively. Spleen smear observation and liver histopathological changes showed that all vaccine groups could produce significant immunoprotection against VL and Amastin-Gp63 vaccine was the best. In conclusion, our work demonstrated that the three dominant multi-epitopes Amastin-Kmp-11, Amastin-Gp63 and Kmp-11-Gp63 DNA prime-protein boost vaccines might be new vaccine candidates for VL, and the Amastin-Gp63 vaccine have best efficacy.


Assuntos
Epitopos/imunologia , Imunidade , Imunização Secundária , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/imunologia , Proteínas de Protozoários/imunologia , Vacinas de DNA/imunologia , Animais , Sítios de Ligação , Citocinas/sangue , Epitopos/química , Feminino , Imunoglobulina G/sangue , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Fígado/patologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Parasitos/fisiologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes/imunologia , Baço/parasitologia
18.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204358

RESUMO

Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different Leishmania strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of L. amazonensis and L. infantum, respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against L. infantum. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by L. amazonensis, which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of Leishmania-infected macrophages to UA led to a significant different production in the cytokine levels depending on the Leishmania strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.


Assuntos
Antiprotozoários/administração & dosagem , Leishmania infantum/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Triterpenos/administração & dosagem , Administração Tópica , Animais , Antiprotozoários/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Infusões Parenterais , Leishmaniose Visceral/parasitologia , Fígado/efeitos dos fármacos , Fígado/parasitologia , Masculino , Mesocricetus , Camundongos , Phytolaccaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Baço/efeitos dos fármacos , Baço/parasitologia , Triterpenos/farmacologia
19.
Sci Rep ; 10(1): 3865, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123265

RESUMO

Previous studies have reported activation of the B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system in T independent immunity against malaria infection. Plasmodium falciparum (P. falciparum) infected animal model is not feasible. Therefore, little is known about the occurrence of BAFF/APRIL system and changes in falciparum lymphoid tissues. This study aimed to investigate the expression of BAFF/APRIL system components in lymphoid tissues from P. falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. Normal spleens and bacterially infected tonsils served as controls. The protein and/or mRNA expression of BAFF/APRIL and their cognate receptors, BAFF-R, TACI and BCMA, were determined by immunohistochemistry and RT-qPCR, respectively. The spleens of the patients exhibited significantly higher BAFF-R protein expression than normal spleens. Although without appropriate control, BCMA protein was markedly observed only in the lymph nodes. BAFF and BCMA mRNA levels were also significantly elevated in the spleen tissues of the patients compared with normal spleens. The overall BAFF-R protein levels in the lymphoid tissues of the patients correlated positively with parasitaemia. These findings are the first to confirm that BAFF/APRIL system activation in lymphoid tissues and is positively correlated with the parasitaemia levels in falciparum malaria.


Assuntos
Fator Ativador de Células B/metabolismo , Proteínas de Ligação a DNA/metabolismo , Linfonodos/metabolismo , Malária Falciparum/metabolismo , Plasmodium falciparum/metabolismo , Baço/metabolismo , Fatores de Transcrição/metabolismo , Receptor do Fator Ativador de Células B/biossíntese , Antígeno de Maturação de Linfócitos B/biossíntese , Regulação da Expressão Gênica , Humanos , Linfonodos/parasitologia , Linfonodos/patologia , Malária Falciparum/patologia , Baço/parasitologia , Baço/patologia , Proteína Transmembrana Ativadora e Interagente do CAML/biossíntese
20.
Parasite Immunol ; 42(5): e12706, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32119124

RESUMO

To provide useful information based on the macropathology, histopathology and immunohistochemical investigation in the spleens of dogs with Babesia rossi infection. Control spleens were collected from four healthy dogs euthanized for welfare reasons. Nine dogs that died naturally because of a mono-infection with Babesia rossi were selected for the diseased group. One haematoxylin-and-eosin-stained section of splenic tissue from each of the infected and control dogs was examined under the light microscope. Immunohistochemical markers were applied to characterize different immunocyte populations. The application of analytic software enabled semi-quantitative comparison of leucocyte subpopulations. Routine splenic histopathology revealed diffuse intermingling of white and red pulp from infected dogs with a clear loss of distinction between these zones. Immunohistochemistry revealed an increase in the proportion of tissue resident and bone marrow origin macrophages in the infected spleens. Apart from a few remnant lymphocytes within the peri-arteriolar lymphatic sheaths and follicles, the majority of the immunocytes redistributed to the red pulp, supporting the observation of white and red pulp intermingling. The majority of our findings are in agreement with histomorphological descriptions of the spleen in a variety of noncanid mammalian hosts with lethal malaria or babesiosis.


Assuntos
Babesia/fisiologia , Babesiose/patologia , Doenças do Cão/patologia , Baço/patologia , Animais , Babesiose/imunologia , Babesiose/parasitologia , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Leucócitos/imunologia , Leucócitos/parasitologia , Linfócitos/imunologia , Linfócitos/parasitologia , Baço/imunologia , Baço/parasitologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...