Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Mediators Inflamm ; 2020: 9278931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192178

RESUMO

Localized cutaneous leishmaniasis (LCL) caused by Leishmania (Viannia) panamensis is an endemic disease in Panama. This condition causes ulcerated skin lesions characterized by a mixed Th1/Th2 immune response that is responsible for disease pathology. However, the maintenance of the in situ inflammatory process involves other elements, such as Th17 and inflammasome responses. Although these processes are associated with parasite elimination, their role in the increase in disease pathology cannot be discarded. Thus, the role in Leishmania infection is still unclear. In this sense, the present study aimed at characterizing the Th17 and inflammasome responses in the skin lesions of patients with LCL caused by L. (V.) panamensis to help elucidate the pathogenesis of this disease in Panama. Th17 and inflammasome responses were evaluated by immunohistochemistry (IHQ) in 46 skin biopsies from patients with LCL caused by L. (V.) panamensis. The Th17 immune response was assessed using CD3, CD4, RoRγt, IL-17, IL-6, IL-23, and TGF-ß1 antibodies, and the inflammasome response was assessed by IL-1ß, IL-18, and caspase-1 antibodies. The presence of the Th17 and inflammasome responses was evidenced by a positive reaction for all immunological markers in the skin lesions. An inverse correlation between the density of amastigotes and the density of RoRγt+, IL-17+, IL-1ß +, and caspase-1+ cells was observed, but no correlation between Th17 and the inflammasome response with evolutionary disease pathology was reported. These data showed the participation of Th17 cells and the inflammasome in the inflammatory response of the skin lesions of LCL caused by L. (V.) panamensis infection. These results suggest a role in the control of tissue parasitism of IL-17 and the activation of the NLRP3 inflammasome dependent on IL-1ß but cannot exclude their role in the development of disease pathology.


Assuntos
Inflamassomos/metabolismo , Leishmania/metabolismo , Leishmaniose Cutânea/metabolismo , Pele/metabolismo , Células Th17/citologia , Adulto , Idoso , Animais , Biópsia , Feminino , Humanos , Inflamação , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Panamá/epidemiologia , Pele/patologia , Adulto Jovem
2.
Mediators Inflamm ; 2016: 7068287, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27073297

RESUMO

Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.


Assuntos
Células Dendríticas/metabolismo , Leishmania braziliensis/patogenicidade , Leishmania/patogenicidade , Linfonodos/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/imunologia , Citometria de Fluxo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Leishmania/imunologia , Leishmania braziliensis/imunologia , Linfonodos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
3.
Parasite Immunol ; 37(8): 407-16, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26040192

RESUMO

The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD)-encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-γ(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+)IL-4(+), CD8(+)IFN-γ(+) and CD8(+)IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-γ and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-γ possibly accounted for the decreased skin parasitism observed in immunized animals.


Assuntos
Leishmania mexicana/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose/imunologia , Vacinas de DNA/imunologia , Animais , Citocinas/imunologia , Imunização , Imunoglobulina G/imunologia , Interferon gama/imunologia , Interleucina-4/imunologia , Leishmaniose/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Superóxido Dismutase/genética , Subpopulações de Linfócitos T/imunologia
4.
Vet Parasitol ; 205(3-4): 444-50, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25257505

RESUMO

We investigated the performance of the DPP(®) canine visceral leishmaniasis (CVL) rapid test, a novel immunochromatographic assay launched by BioManguinhos (Brazil), which was recently included in the new Brazilian protocol for screening CVL in serological surveys. The present study compared the DPP(®) with the ELISA and IFA produced by BioManguinhos (Brazil) both with L. major-like antigens and with in-house tests using Leishmania infantum chagasi (in-house ELISA and in-house IFA). We analyzed the sera from clinically symptomatic (n=47) and asymptomatic (n=38) infected dogs from an endemic area of CVL, as well as from healthy (n=18) dogs, in addition to the sera of dogs (n=81) infected with other pathogens. The DPP(®) and the in-house ELISA showed a sensitivity of 90.6% and 94.1%, respectively, and specificity of 95.1% and 97.5%, respectively, and both presented cross-reactivity only with the sera of dogs with babesiosis, 44% for the DPP(®) and 22% for the in-house ELISA. The clinical groups were detected equally by the two assays. The ELISA BioManguinhos, IFA BioManguinhos, and in house-IFA showed a good sensitivity, 90.6%, 96.5% and 89.4%, respectively, but very low specificity, 77.8%, 69.1% and 65.8%, respectively, due to the high cross-reactivity with the sera from the animals harboring other pathogens. The in-house ELISA provided the highest accuracy (95.8%), followed by the DPP(®) (92.7%), ELISA BioManguinhos (84.3%), IFA BioManguinhos (83.1%), and in-house IFA (78.0%). The simultaneous use of the DPP(®) and ELISA BioManguinhos reached a sensitivity of 99.1% and 82.1% when used sequentially. In conclusion, the DPP(®) performed well as serological test for CVL, and detected both asymptomatic and symptomatic dogs in equal proportions. Although its sensitivity is not ideal yet, discarding the IFA and including the DPP(®) improved the accuracy of the new Brazilian CVL diagnostic protocol, particularly of detecting truly infected dogs. Moreover, considering the higher specificity of DPP(®) (95.1% vs 77.8%), positive predictive value (95.1% vs 81.1%) and positive likelihood value (18.3% vs 4.1%) in comparison with the ELISA BioManguinhos, the use of DPP(®) as a confirmatory test instead of a screening test is suggested.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Doenças do Cão/epidemiologia , Leishmania infantum/imunologia , Leishmaniose Visceral/diagnóstico , Animais , Brasil , Cromatografia de Afinidade , Reações Cruzadas , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Técnica Indireta de Fluorescência para Anticorpo , Leishmania infantum/isolamento & purificação , Coelhos , Sensibilidade e Especificidade , Testes Sorológicos/veterinária , Fatores de Tempo
5.
Arch Dermatol Res ; 306(2): 163-71, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23922083

RESUMO

Regulatory T cells (Tregs) are a unique population of CD25+CD4+ T cells that regulate innate and adaptive immune responses and have the ability to control the excessive or misdirected effects of the immune system. This modulation involves different mechanisms, such as the suppression of T cell proliferation and cytokine production, the secretion of suppressive cytokines (IL-10 and TGF-ß) and the induction of effector T cell apoptosis in humans with infectious diseases such as Leishmania infections. The aim of this study was to evaluate the expression of Foxp3, IL-10 and TGF-ß through immunohistochemistry in 22 skin biopsies of patients with localized cutaneous leishmaniasis (LCL) caused by Leishmania (Viannia) spp. from an endemic area in pre-Amazonian area of Maranhão State, Brazil. The density of these markers was also analyzed according to the species of parasite and the progression of the disease. The cellular density was 234 cells/mm(2) for Foxp3+ cells, 357 cells/mm(2) for TGF-ß+ cells and 648 cells/mm(2) for IL-10+ cells in the studied skin lesions. The analysis of the cellular density of these immunological markers in relation to the species of Leishmania demonstrated that lesions caused by L. (V.) braziliensis had a lower density of Foxp3+ cells than lesions caused by L. (Viannia) spp. The expression of IL-10 was also lower in lesions caused by L. (V.) braziliensis. There were no significant differences in TGF-ß expression between the two groups. The evaluation of these markers according to the progression of the disease did not reveal any significant differences. These findings suggest that Treg Foxp3+ cells, IL-10, and TGF-ß play important roles in the immunopathogenesis of LCL and that these roles differ depending on the causal Leishmania species.


Assuntos
Biomarcadores/metabolismo , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/imunologia , Pele/metabolismo , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Brasil , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interleucina-10/metabolismo , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Pele/parasitologia , Pele/patologia , Especificidade da Espécie , Fator de Crescimento Transformador beta/metabolismo , Adulto Jovem
6.
Parasite Immunol ; 34(8-9): 395-403, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22587683

RESUMO

The expression of Langerhans cell (LC) and dermal dendritic cell (dDC) as well as T CD4(+) and CD8(+) immune responses was evaluated in the skin of BALB/c mice experimentally infected by L. (L.) amazonensis (La) and L. (V.) braziliensis (Lb). At 4th and 8th weeks post infection (PI), skin biopsies were collected to determine the parasite load and CD207(+), CD11c(+), CD4(+), CD8(+), iNOS(+) cellular densities. Cytokine (IFN-γ, IL-4 and IL-10) profiles were also analysed in draining lymph node. At 4th week, the densities of CD207(+) and CD11c(+) were higher in the La infection, while in the Lb infection, these markers revealed a significant increase at 8th week. At 4th week, CD4(+) and CD8(+) were higher in the La infection, but at 8th week, there was a substantial increase in both markers in the Lb infection. iNOS(+) was higher in the Lb infection at 4th and 8th weeks. In contrast, the parasite load was higher in the La infection at 4th and 8th weeks. The concentration of IFN-γ was higher in the Lb infection, but IL-4 and IL-10 were higher in the La infection at 4th and 8th weeks. These results confirm the role of the Leishmania species in the BALB/c mice disease characterized by differences in the expression of dendritic cells and cellular immune response.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/parasitologia , Perfilação da Expressão Gênica , Leishmania braziliensis/imunologia , Leishmania mexicana/imunologia , Animais , Antígenos CD/biossíntese , Biópsia , Citocinas/biossíntese , Modelos Animais de Doenças , Leishmaniose/imunologia , Leishmaniose/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/biossíntese , Carga Parasitária , Pele/imunologia , Pele/parasitologia , Fatores de Tempo
7.
Scand J Immunol ; 70(4): 389-95, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19751274

RESUMO

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated subcutaneously into the hind footpads or into the ear dermis with 10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors.


Assuntos
Leishmania mexicana , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Glândulas Salivares/química , Extratos de Tecidos/imunologia , Animais , Animais de Laboratório , Animais Selvagens , Contagem de Células , Orelha/parasitologia , Orelha/patologia , Feminino , Pé/parasitologia , Pé/patologia , Interferon gama/metabolismo , Interleucinas/metabolismo , Linfonodos/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Neutrófilos/patologia , Psychodidae/química
8.
Parasite Immunol ; 31(8): 423-31, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19646206

RESUMO

The immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis were reviewed in the light of more recent features found in the clinical and immunopathological spectrum of American cutaneous leishmaniasis. It was shown a dichotomy in the interaction between these Leishmania species and human T-cell immune response; while L. (V.) braziliensis shows a clear tendency to lead infection from the localized cutaneous leishmaniasis (LCL), a moderate T-cell hypersensitivity form at the centre of the spectrum, toward to the mucocutaneous leishmaniasis (MCL) at the T-cell hypersensitivity pole and with a prominent Th1-type immune response, L. (L.) amazonensis shows an opposite tendency, leading infection to the anergic diffuse cutaneous leishmaniasis (ADCL) at the T-cell hyposensitivity pole and with a marked Th2-type immune response. Between the central LCL and the two polar MCL and ADCL, the infection can present an intermediary form known as borderline disseminated cutaneous leishmaniasis, characterized by an incomplete inhibition of T-cell hypersensitivity but with a evident supremacy of Th1 over Th2 immune response (Th1 > or = Th2). These are probably the main immunopathogenic competences of L. (V.) braziliensis and L. (L.) amazonensis regarding the immune response dichotomy that modulates human infection outcome by these Leishmania parasites.


Assuntos
Leishmania braziliensis/patogenicidade , Leishmania/patogenicidade , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Pele/parasitologia , Animais , Divisão Celular , Humanos , Leishmaniose Cutânea/patologia , Pele/patologia , Especificidade da Espécie , Células Th1/citologia , Células Th1/imunologia , Células Th2/imunologia , Virulência
9.
Parasitol Res ; 101(5): 1365-71, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17659386

RESUMO

In this study, we compared the anti-leishmanial activity of three crotalic venoms (Crotalus durissus terrificus-Cdt, Crotalus durissus cascavella-Cdca, and Crotalus durissus collilineatus-Cdcol). Different concentrations of each venom incubated with Leishmania (Leishmania) amazonensis promastigotes were used. Cdt venom exhibited a higher anti-leishmanial activity (Inhibitory concentration-IC50-value of 4.70+/-1.72 microg/ml) in comparison with that of Cdca venom (IC50 value of 9.41+/-1.21 microg/ml), while Cdcol venom increased parasite numbers in 50% at a concentration of 44.30+/-2.18 microg/ml. In addition, this venom showed a low anti-leishmanial activity in higher concentrations (IC50 value of 281.00+/-9.50 microg/ml). The main fractions of Cdca venom were isolated and assayed under similar conditions used for assessing crude venom. The most active fractions were gyroxin and crotamine that had IC50 values of 3.80+/-0.52 microg/ml and 19.95+/-4.21 microg/ml, respectively. Convulxin also inhibited parasite growth rate, although this effect was not dose-dependent. Crotoxin was the least effective fraction with an IC50 value of 99.80+/-2.21 microg/ml. None of the protein fractions presented cytotoxic effects against J774 cells in culture. In vivo assays using BALB/c mice revealed that crotoxin and crotamine were the main toxic fractions. In conclusion, C. durissus cascavella venom has three main fractions with anti-leishmanial activity. These results open new possibilities to find proteins that might be used as possible agents against cutaneous leishmaniasis.


Assuntos
Antiprotozoários/toxicidade , Venenos de Crotalídeos/toxicidade , Leishmania/efeitos dos fármacos , Animais , Antiprotozoários/química , Linhagem Celular , Venenos de Crotalídeos/química , Venenos de Crotalídeos/isolamento & purificação , Crotoxina/isolamento & purificação , Crotoxina/toxicidade , Concentração Inibidora 50 , Lectinas Tipo C/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Intoxicação
10.
Parasitol Res ; 101(3): 677-80, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17390147

RESUMO

The crude methanolic extract from leaves of Jacaranda puberula showed activity against Leishmania (Leishmania) amazonensis. The extract presented active against promastigote forms with an inhibitory concentration 50% (IC(50)) value of 88.0 mug/ml, but only moderated activity against amastigote forms; however in higher concentrations the extract showed cytotoxic effects. The bio-guided chromatographic fractionation the crude methanolic extract against amastigotes yielded a fraction with an IC(50) value of 14.0 mug/ml (without cytotoxic activity) in relation to the crude extract (IC(50) value, 359.0 microg/ml). These data indicate that J. puberula leaves contain active compounds, which should be further investigated for the development of new potential drugs against cutaneous leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Bignoniaceae/química , Leishmania/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Células Cultivadas , Leishmania/crescimento & desenvolvimento , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade
11.
Vet Parasitol ; 145(3-4): 245-52, 2007 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-17257764

RESUMO

Aiming to improve the diagnosis of canine leishmaniasis (CanL) in an endemic area of the Northwest region of São Paulo State, Brazil, the efficacy of parasitological, immunological and molecular diagnostic methods were studied. Dogs with and without clinical signs of the disease and positive for Leishmania, by direct parasite identification on lymph node smears and/or specific antibody detection by ELISA, were selected for the study. According to the clinical signs, 89 dogs attending the Veterinary Hospital of UNESP in Araçatuba (SP, Brazil) were divided into three groups: symptomatic (36%), oligosymptomatic (22%) and asymptomatic (22%). Twenty-six dogs from an area non-endemic for CanL were used as negative controls (20%). Fine-needle aspiration biopsies (FNA) of popliteal lymph nodes were collected and Diff-Quick-stained for optical microscopy. Direct immunofluorescence, immunocytochemistry and parasite DNA amplification by PCR were also performed. After euthanasia, fragments of popliteal lymph nodes, spleen, bone marrow and liver were collected and processed for HE and immunohistochemistry. Parasite detection by both HE and immunohistochemistry was specifically more effective in lymph nodes, when compared with the other organs. Immunolabeling provided higher sensitivity for parasite detection in the tissues. In the symptomatic group, assay sensitivity was 75.61% for direct parasite search on Diff-Quick-stained FNAs, 92.68% for direct immunofluorescence, 92.68% for immunocytochemistry and 100% for PCR; the corresponding values in the other clinical groups were: 32, 60, 76 and 96% (oligosymptomatic), and 39.13, 73.91, 100 and 95.65% (asymptomatic). Results of the control animals from the CanL non-endemic area were all negative, indicating that the methods used were 100% specific.


Assuntos
Doenças do Cão/diagnóstico , Leishmaniose Visceral/veterinária , Animais , Biópsia por Agulha Fina/veterinária , Medula Óssea/parasitologia , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Técnica Direta de Fluorescência para Anticorpo/veterinária , Imuno-Histoquímica/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Fígado/parasitologia , Linfonodos/parasitologia , Reação em Cadeia da Polimerase/veterinária
12.
Scand J Immunol ; 62(4): 334-41, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16253120

RESUMO

To study the role of Natural Killer (NK) cells in Leishmania infection, peritoneal macrophages from BALB/c mice were infected with Leishmania (Leishmania) amazonensis promastigotes and incubated with interleukin-2 (IL-2)-activated NK (A-NK) cells at different ratios of A-NK cells to infected macrophages (5:1, 1:1, 0.2:1). The A-NK cells were added either together with the parasites (0-h group) or 24 h later (24-h group). Morphological studies of the cultures revealed predominance of parasitic debris within macrophages that were in close contact with A-NK cells and the decrease in parasite recovery was directly proportional to the A-NK cell concentration used. Interferon-gamma (IFN-gamma) and IL-12 were detected in the supernatant at levels proportional to the A-NK cell concentration used. No significant difference was observed between the groups with respect to NO levels in the culture supernatant. When A-NK cells were added directly to the L. (L.) amazonensis promastigote cultures, the parasite recovery decreased proportional to the number of A-NK cells added. In vivo studies demonstrated smaller lesion sizes in animals inoculated with both parasites and A-NK cells compared with parasites alone. Histopathology of the skin lesions from animals receiving A-NK cells together with the parasites showed moderate parasitism and a nodular inflammatory infiltrate formed by mononuclear cells and a few vacuolized macrophages. In contrast, animals inoculated only with the parasites showed a highly parasitized dermis with infiltration of intensely vacuolized macrophages. These results demonstrate the role of A-NK cells in parasite lysis and in resistance of macrophages to L. (L.) amazonensis in the early phase of infection.


Assuntos
Interleucina-2/fisiologia , Células Matadoras Naturais/imunologia , Leishmaniose/imunologia , Ativação Linfocitária/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/parasitologia , Animais , Interferon gama/metabolismo , Interleucina-12/metabolismo , Células Matadoras Naturais/metabolismo , Leishmania/imunologia , Leishmania/ultraestrutura , Leishmaniose/metabolismo , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nitritos/metabolismo
13.
Braz J Med Biol Res ; 37(3): 427-34, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15060713

RESUMO

Complement-depleted and -non-depleted BALB/c mice were inoculated with Leishmania (Leishmania) amazonensis promastigotes into the hind footpad to study the role of the complement system in cutaneous leishmaniasis. Total serum complement activity was measured by hemolytic assay and C3 fragment deposit at the inoculation site was determined by direct immunofluorescence in the early period of infection, i.e., at 3, 24, 48 h and 7 days post-infection. The inflammatory reaction and the parasite burden were evaluated in the skin lesion at 7 and 30 days post-infection. Total serum complement activity decreased in the early phase of infection, from 3 to 24 h, in non-depleted mice compared to non-infected and non-depleted mice. C3 fragment deposit at the site of parasite inoculation was present throughout the period of infection in non-depleted mice. In contrast, no C3 fragment deposit was observed at the inoculation site in complement-depleted mice. Complement-depleted mice showed a significant decrease in the inflammatory response and a significant increase in the number of parasites (70.0 +/- 5.3 vs 5.3 +/- 1.5) at 7 days of infection (P<0.05). A higher number of parasites were also present at 30 days of infection at the inoculation site of complement-depleted mice (78.5 +/- 24.9 vs 6.3 +/- 5.7). These experiments indicate that complement has an important role at the beginning of experimental cutaneous leishmaniasis caused by L. (L.) amazonensis by controlling the number of parasites in the lesion.


Assuntos
Proteínas do Sistema Complemento/fisiologia , Leishmania , Leishmaniose Cutânea/imunologia , Animais , Ativação do Complemento , Complemento C3/fisiologia , Ensaio de Atividade Hemolítica de Complemento , Leishmaniose Cutânea/parasitologia , Depleção Linfocítica , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
Braz. j. med. biol. res ; 37(3): 427-434, Mar. 2004. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-356627

RESUMO

Complement-depleted and -non-depleted BALB/c mice were inoculated with Leishmania (Leishmania) amazonensis promastigotes into the hind footpad to study the role of the complement system in cutaneous leishmaniasis. Total serum complement activity was measured by hemolytic assay and C3 fragment deposit at the inoculation site was determined by direct immunofluorescence in the early period of infection, i.e., at 3, 24, 48 h and 7 days post-infection. The inflammatory reaction and the parasite burden were evaluated in the skin lesion at 7 and 30 days post-infection. Total serum complement activity decreased in the early phase of infection, from 3 to 24 h, in non-depleted mice compared to non-infected and non-depleted mice. C3 fragment deposit at the site of parasite inoculation was present throughout the period of infection in non-depleted mice. In contrast, no C3 fragment deposit was observed at the inoculation site in complement-depleted mice. Complement-depleted mice showed a significant decrease in the inflammatory response and a significant increase in the number of parasites (70.0 ± 5.3 vs 5.3 ± 1.5) at 7 days of infection (P < 0.05). A higher number of parasites were also present at 30 days of infection at the inoculation site of complement-depleted mice (78.5 ± 24.9 vs 6.3 ± 5.7). These experiments indicate that complement has an important role at the beginning of experimental cutaneous leishmaniasis caused by L. (L.) amazonensis by controlling the number of parasites in the lesion.


Assuntos
Animais , Masculino , Camundongos , Proteínas do Sistema Complemento , Leishmania , Leishmaniose Cutânea , Complemento C3 , Ensaio de Atividade Hemolítica de Complemento , Técnica Direta de Fluorescência para Anticorpo , Leishmaniose Cutânea , Depleção Linfocítica , Camundongos Endogâmicos BALB C
15.
Int J Exp Pathol ; 81(4): 249-55, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10971746

RESUMO

While the control or progression of leishmaniasis depends on host immune responses, the initial inflammatory process represents a key event. This process involves the participation of several cytokines and growth factors induced during inflammation as well as factors already present at the site of infection such as insulin-like growth factor (IGF)-I. We have previously demonstrated a potential role for IGF-I in experimental cutaneous leishmaniasis based on the significant increase in lesion size seen in mice injected with Leishmania promastigotes preactivated with IGF-I. In the present study we show that preactivation of Leishmania (Leishmania) amazonensis promastigotes with IGF-I induces an increase in the actual number of parasites at the lesion site from seven days postinfection, in addition to a more intense inflammatory infiltrate. There was a higher numerical density of polymorphonuclear neutrophils from 3 to 24 h, and of mononuclear cells from 48 h of infection onward. A higher density of polymorphonuclear neutrophils and mononuclear cells harboring parasites was also observed. The most important observation, however, was that more parasites per cell were present, revealing that IGF-I appears to favour parasite growth within the macrophages. These results strongly suggest an important role for IGF-I in the development of cutaneous leishmaniasis, where it influences both the inflammatory process and parasite growth.


Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Animais , Interações Hospedeiro-Parasita/efeitos dos fármacos , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/patologia , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/parasitologia , Proteínas Recombinantes/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-10513065

RESUMO

Mega-organs, primarily in the digestive tract, are well known to occur in chronic Chagas disease. Acute experimental infection with Trypanosoma cruzi results in parasitism of a wide range of cells, tissues, and organs, including the urinary bladder. Infection of BALB/c mice with 100,000 bloodstream forms of the Y strain of T. cruzi induced acute infection with intense parasitism of all layers of the urinary bladder. Parasites were found in the mucosa, lamina propria, muscular, adventitial connective, and fat tissue. Desquamate epithelial cells with amastigotes in the bladder lumen were also found. After 60 days of infection, mice inoculated with 50 bloodstream forms developed dilated, thin-walled bladders that had inflammatory infiltrates and foci of fibrosis replacing areas of damaged muscular layer. These lesions result from direct damage to the muscle fibers by the T. cruzi, leading to myosites, muscle damage, and scarring. Direct damage of paraganglia cells secondary to parasitism, leading to dilatation, damage of muscle fibers, and scarring with replacement of muscular tissue with connective tissue, should also be considered as a cause of functional disturbance of the urinary bladder.


Assuntos
Doença de Chagas/patologia , Trypanosoma cruzi , Bexiga Urinária/parasitologia , Doenças Urológicas/parasitologia , Doença Aguda , Animais , Camundongos , Camundongos Endogâmicos BALB C , Bexiga Urinária/patologia
17.
Braz J Med Biol Res ; 32(3): 323-5, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10347791

RESUMO

In order to study the role of natural killer (NK) cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania) amazonensis (HSJD-1 strain). 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 10(6) spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 10(6) spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection.


Assuntos
Células Matadoras Naturais/efeitos da radiação , Leishmaniose Cutânea/radioterapia , Radioisótopos de Estrôncio/uso terapêutico , Animais , Interferon-alfa/biossíntese , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C
18.
Braz. j. med. biol. res ; 32(3): 323-5, Mar. 1999.
Artigo em Inglês | LILACS | ID: lil-230460

RESUMO

In order to study the role of natural killer (NK) cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania) amazonensis (HSJD-1 strain). 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 106 spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 106 spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection


Assuntos
Animais , Camundongos , Células Matadoras Naturais/efeitos da radiação , Leishmaniose Cutânea/radioterapia , Radioisótopos de Estrôncio/uso terapêutico , Interferon-alfa/biossíntese , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/radioterapia , Depleção Linfocítica , Camundongos Endogâmicos BALB C , Radioisótopos de Estrôncio/uso terapêutico
20.
Int J Exp Pathol ; 77(1): 15-24, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8664142

RESUMO

Tecidual reaction at the inoculation site of L. (L.)chagasi promastigotes in hamsters depleted and non-depleted of complement was studied within 2, 6, 12, 24, 48 and 72 hours of infection. The inflammatory reaction was characterized by early predominance of polymorphonuclear cells (PMN) at 2, 6 and 12 hours of infection, mixed infiltrate of PMN and mononuclear cells (MN) at 24 hours, followed by predominance of MN at 48 and 72 hours after infection. The group depleted of complement showed a higher number of PMN at 2 hours and lower numbers of MN at 72 hours after infection (P < 0.0001). In the depleted group the phagocytosis by PMN was lower at 2 and 24 hours and by MN was lower at 24, 48 and 72 hours after infection. Electron microscopy showed extracellular intact and degenerated parasites, and lysed intracellular parasites, in PMN; and, rarely, preserved intracellular parasites in MN at 2, 6 and 12 hours after infection. The groups examined at 24, 48 and 72 hours of infection showed only cellular and parasite debris in mononuclear inflammatory cells. C3b deposits were detected by immunofluorescence in the interstitium and in the cytoplasm of inflammatory cells in non-depleted group at 2, 6 and 12 hours of infection. No immunoglobulin was detected in either group. Visceralization was detected 240 days after infection. The complement system has an important role in the inflammatory reaction and phagocytosis. The ultrastructural findings showed that the escape of the parasite probably occurs soon after inoculation.


Assuntos
Complemento C3/imunologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/imunologia , Dermatopatias Parasitárias/imunologia , Pele/imunologia , Doença Aguda , Animais , Cricetinae , Interações Hospedeiro-Parasita/imunologia , Leishmania infantum/ultraestrutura , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Macrófagos/imunologia , Masculino , Mesocricetus , Microscopia Eletrônica , Neutrófilos/imunologia , Fagocitose , Dermatopatias Parasitárias/parasitologia , Dermatopatias Parasitárias/patologia , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...