RESUMO
Leptospirosis is globally widespread neglected disease, affecting most mammalian species. Clinical signs can be confused with other diseases which make the diagnosis and treatment difficult. Chemokines and cytokines are known for their role in the inflammatory and immune response to infections. The profile determination of chemokines' expressions in the course of infection may elucidate the defense mechanisms of the host and support the search for effective treatment strategies. We investigated the mechanisms of innate immunity through the comparison of chemokines induced during infection with L. interrogans in mice with different levels of susceptibility. We used lung and spleen tissues samples of mice from C3H/HeJ, C3H/HePas and Balb/c, respectively sensitive, intermediate susceptibility and resistant to the pathogen. The inoculation of L. interrogans in C3H/HeJ mice led a comparatively smaller change in chemokines expression in both spleen and lung tissues. In samples from spleens and lungs of C3H/HePas and Balb/c the higher increases occurred on CXCL9, CXCL16, CXCL5, CCL8 and CCL5 in Balb/c. Given the same genetic background, the differences in the responses of C3H/HePas compared to C3H/HeJ mice strongly suggest the role of chemokines for the survival of parental strain. Therefore, the greatest increase in CXC chemokines appears to be efficient to induce migration of cells to the secondary lymphoid organs and affected tissues, which is important to control infection. Overall, CXC chemokines are important for the activation and attraction of T cell and may influence the course and control of the infection in resistant Balb/c mice.
Assuntos
Quimiocinas/metabolismo , Leptospira/imunologia , Leptospirose/patologia , Pulmão/fisiologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Células Cultivadas , Progressão da Doença , Regulação Bacteriana da Expressão Gênica , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Interações Hospedeiro-Patógeno , Imunidade Inata , Mediadores da Inflamação/metabolismo , Leptospirose/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Rotavirus is an important aetiological agent for severe diarrhoea in infants and young children worldwide. Anti-rotavirus antibodies in human colostrum and milk may interfere with rotavirus vaccination seroconversion. AIMS: To verify the presence of anti-rotavirus secretory IgA antibodies (SIgA) and the neutralizing capacity of 30 colostrum and 30 milk samples from Brazilian women in two different centres and analyze their persistence throughout lactation. METHODS: Colostrum and milk samples from healthy nursing mothers were tested for the presence of anti-rotavirus SIgA using conventional ELISA and their capacity to neutralize rotavirus using MA-104 cell cultures. Total IgA concentrations and anti-rotavirus SIgA levels were measured in samples collected from three mothers during 90 or 240 days of the lactation period. RESULTS: Colostrum samples showed higher levels of anti-rotavirus SIgA and higher neutralizing ability than in milk. However, these antibodies levels were not statistically different. In addition, there was no correlation between antibody levels and the neutralizing activity observed in colostrum and milk samples. Follow-up of three mothers demonstrated the persistence of anti-rotavirus and total IgA levels throughout lactation. CONCLUSIONS: These results support the encouragement of breastfeeding as a mechanism of protection against rotavirus infection in lactating infants. Components other than SIgA antibodies might play an important role in virus neutralization.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Colostro/imunologia , Imunoglobulina A Secretora/imunologia , Leite Humano/imunologia , Rotavirus/imunologia , Anticorpos Neutralizantes/análise , Anticorpos Antivirais/análise , Brasil , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A Secretora/análise , Testes de NeutralizaçãoRESUMO
We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax AIRmin) F2 intercrossmouse population derived from non-inbred parents, by association analysis in the absence of pedigree information. Using 1064 autosomal single nucleotide polymorphisms (SNPs), we clustered the intercross population into 12 groups of genetically related individuals. Association analysis adjusted for genetic clusters allowed to identify two loci, inflammatory response modulator 1 (Irm1) on chromosome 7 previously detected by genetic linkage analysis in the F2 mice, and a new locus onchromosome 5 (Irm2), linked to the number of infiltrating cells in subcutaneous inflammatory exudates (Irm1: P»6.3 10 7; Irm2: P»8.2 10 5) and interleukin 1 beta (IL-1b) production (Irm1: P»1.9 10 16; Irm2: P»1.1 10 6). Use of a polygenic model based on additive effects of the rare alleles of 15 or 18 SNPs associated at suggestive genome-wide statistical threshold(Po3.4 10 3) with the number of infiltrating cells or IL-1b production, respectively, allowed prediction of the inflammatory response of progenitor AIR mice. Our findings suggest the usefulness of association analysis in combination with genetic clustering to map loci affecting complex phenotypes in non-inbred animal species.
Assuntos
Camundongos , Análise por Conglomerados , Hereditariedade/genética , Hereditariedade/imunologia , Ligação Genética/genética , Reação de Fase Aguda/imunologia , Análise Citogenética/métodos , Polimorfismo de Nucleotídeo Único/imunologiaRESUMO
Periodontitis (PD) and rheumatoid arthritis (RA) have been found to be clinically associated and to share the chronic nature of the inflammatory reaction associated with bone resorption activity. However, the mechanisms underlying such association are unknown. Therefore, we examined the basis of Actinobacillus actinomycetemcomitans- and Porphyromonas gingivalis-induced PD and pristane-induced arthritis (PIA) interaction in mice. Higher severity PD in the genetically inflammation prone acute inflammatory reactivity maximum (AIRmax) mice strain was associated with higher levels of TNF-alpha, IL-1beta, IL-17, matrix metalloproteinase (MMP)-13, and RANKL, whereas PD/PIA co-induction resulted in even higher levels of IL-1beta, IFN-gamma, IL-17, RANKL, and MMP-13 levels. Conversely, PD/PIA co-induction in AIRmin strain did not alter the course of both pathologies. PIA/PD co-induction resulted in altered expression of T-cell subsets transcription factors expression, with T-bet and RORgamma levels being upregulated, whereas GATA-3 levels were unaltered. Interestingly, PIA induction resulted in alveolar bone loss, such response being highly dependent on the presence of commensal oral bacteria. No differences were found in PIA severity parameters by PD co-induction. Our results show that the interaction between experimental PD and arthritis in mice involves a shared hyper-inflammatory genotype and functional interferences in innate and adaptive immune responses.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Genótipo , Mediadores da Inflamação/fisiologia , Periodontite/genética , Periodontite/imunologia , Animais , Artrite Reumatoide/patologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Camundongos , Camundongos Transgênicos , Periodontite/patologiaRESUMO
The goal in transplantation is to obtain immunosuppressant combinations that decrease the incidence of acute and chronic rejection but cause fewer side effects. FTY720 is a new immunomodulator that prevents experimental allograft rejection without inhibiting T-cell activation. It is currently under clinical investigation for multiple sclerosis. We investigated whether FTY720 in combination with sirolimus (SRL) could cause renal toxicity in C57BL/6 mice when administered for 21 days. Serum creatinine and 24-hour urinary creatinine concentrations were assessed by enzymatic colorimetric assays. Urinary protein concentration was measured by the Bradford protein assay. Whereas serum creatinine levels were increased in FTY720 + SRL-treated animals, there were no changes in urinary volume, urinary protein levels, serum urea concentration, creatinine clearance, and kidney structure. Our findings suggested that FTY720 monotherapy for multiple sclerosis and other diseases could play an important immunomodulatory role without causing the side effects frequently observed with other transplantation regimens.
Assuntos
Creatinina/sangue , Imunossupressores/farmacologia , Propilenoglicóis/farmacologia , Sirolimo/farmacologia , Esfingosina/análogos & derivados , Animais , Creatinina/urina , Diurese/efeitos dos fármacos , Cloridrato de Fingolimode , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Transplante de Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Propilenoglicóis/efeitos adversos , Propilenoglicóis/uso terapêutico , Proteinúria , Sirolimo/uso terapêutico , Esfingosina/efeitos adversos , Esfingosina/farmacologia , Esfingosina/uso terapêuticoRESUMO
The role of innate immune responses in protection against leptospirosis remains unclear. We examined the expression of the chemokines CCL2/JE (MCP-1), CCL3/MIP-1á (MIP-1á) and CXCL1/KC (IL-8) regarding resistance and susceptibility to leptospirosis in experimental mice models BALB/c and C3H/HeJ, respectively. A virulent strain of Leptospira interrogans serovar Copenhageni was used in this study. Twenty-five animals of each mouse strain of C3H/HeJ and BALB/c, were infected intraperitoneally with 106 cells. Five un-infected animals of each strain were kept as control. Mortality of C3H/HeJ mouse was observed while BALB/c mice were asymptomatic. The presence of leptospire DNA in tissues of infected animals was demonstrated by PCR. Chemokines were measured in serum, spleen, liver, kidney and lung of both strains of animals using immunoenzymatic assay (ELISA). Elevations in the levels of chemokines MCP-1 and IL-8 occurred in all organs and sera of C3H/HeJ and BALB/c infected mice. The levels of MIP-1á were lower when compared to MCP-1 and IL-8 in all analyzed organs, with a slight increase in liver and kidney. Our results indicate that the expression of inflammatory mediators can vary greatly, depending on the tissue and mouse strains. It is possible that the resistance to Leptospira can be partially correlated to the increase of MIP-1á observed in BALB/c mice, while an increasing and a sustained expression of MCP-1 and IL-8 in the lungs of C3H/HeJ mice can be correlated to the severity and progression of leptospirosis.
Assuntos
Animais , Camundongos , Leptospira interrogans/patogenicidade , Leptospirose/imunologia , Imunidade InataRESUMO
OBJECTIVE: Mice selected for a strong (AIRmax) or weak (AIRmin) acute inflammatory response present different susceptibilities to bacterial infections, autoimmune diseases and carcinogenesis. Variations in these phenotypes have been also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic differences observed in these mice was related to the complement system. MATERIAL: AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1 member (Slc11a1) gene, formerly designated Nramp-1. METHODS AND RESULTS: While no difference in complement activity was detected in sera from AIRmax and AIRmin strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no complement-dependent hemolytic activity. Furthermore, C5 was not found in their sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D) mutation previously described in A/J. Therefore, the C5D allele was fixed in homozygosis in AIRmax(RR) line. CONCLUSIONS: The AIRmax(RR) line is a new experimental mouse model in which a strong inflammatory response can be triggered in vivo in the absence of C5.
Assuntos
Complemento C5 , Inflamação/genética , Camundongos Endogâmicos , Animais , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/imunologia , Ativação do Complemento , Complemento C5/genética , Complemento C5/imunologia , Via Alternativa do Complemento/imunologia , Feminino , Predisposição Genética para Doença , Hemólise , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos/genética , Camundongos Endogâmicos/imunologiaRESUMO
BACKGROUND AND OBJECTIVE: Inflammatory immune reactions that occur in response to periodontopathogens are thought to protect the host against infection, but may trigger periodontal destruction. However, the molecular and genetic mechanisms underlying host susceptibility to periodontal infection and to periodontitis development have still not been established in detail. MATERIAL AND METHODS: In this study, we examined the mechanisms that modulate the outcome of Aggregatibacter (Actinobacillus) actinomycetemcomitans-induced periodontal disease in mice mouse strains selected for maximal (AIRmax) or minimal (AIRmin) inflammatory reactions. RESULTS: Our results showed that AIRmax mice developed a more severe periodontitis than AIRmin mice in response to A. actinomycetemcomitans infection, and this periodontitis was characterized by increased alveolar bone loss and inflammatory cell migration to periodontal tissues. In addition, enzyme-linked immunosorbent assays demonstrated that the levels of the cytokines interleukin-1beta, tumor necrosis factor-alpha and interleukin-17 were higher in AIRmax mice, as were the levels of matrix metalloproteinase (MMP)-2, MMP-13 and receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA levels. However, the more intense inflammatory immune reaction raised by the AIRmax strain, in spite of the higher levels of antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase, did not enhance the protective immunity to A. actinomycetemcomitans infection, because both AIRmax and AIRmin strains presented similar bacterial loads in periodontal tissues. In addition, the AIRmax strain presented a trend towards higher levels of serum C-reactive protein during the course of disease. CONCLUSION: Our results demonstrate that the intensity of the inflammatory immune reaction is associated with the severity of experimental periodontitis, but not with the control of A. actinomycetemcomitans periodontal infection, suggesting that the occurrence of hyperinflammatory genotypes may not be an evolutionary advantage in the complex host-pathogen interaction observed in periodontal diseases.
Assuntos
Infecções por Actinobacillus/imunologia , Aggregatibacter actinomycetemcomitans/imunologia , Perda do Osso Alveolar/imunologia , Periodontite/imunologia , Perda do Osso Alveolar/microbiologia , Animais , Proteína C-Reativa/análise , Movimento Celular/fisiologia , Contagem de Colônia Microbiana , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno , Interleucina-17/análise , Interleucina-1beta/análise , Contagem de Leucócitos , Leucócitos/imunologia , Masculino , Metaloproteinase 13 da Matriz/análise , Metaloproteinase 2 da Matriz/análise , Camundongos , Óxido Nítrico Sintase Tipo II/análise , Osteoprotegerina/análise , Periodontite/sangue , Periodontite/microbiologia , Peroxidase/análise , Ligante RANK/análise , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-3/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax(RR) mice reached 29%, whereas PIA incidence in AIRmax(SS) mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRmin(SS) mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.
Assuntos
Artrite Reumatoide/genética , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença , Inflamação/genética , Terpenos , Alelos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Cromossomos de Mamíferos , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Frequência do Gene , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Locos de Características Quantitativas , Baço/citologiaRESUMO
Enterohaemorrhagic Escherichia coli (EHEC) can cause a variety of human illnesses ranging from uncomplicated diarrhoea to haemorrhagic colitis and haemolytic uremic syndrome. The serotype O157:H7 has been associated with numerous outbreaks worldwide, but in Brazil the infection is rare. Brazilian adults present antibodies reactive with the principal virulence factors of enteropathogenic E. coli (EPEC) that have many genetic and antigenic similarities with EHEC. Lipopolysaccharides (LPS) are components of outer membranes and important virulence factors of Gram-negative bacteria. LPS O111 is present in EPEC and EHEC strains. LPS O157 is found only in EHEC strains, but it has some structural similarities with LPS O55 present in EPEC strains. This study investigates the levels of IgG and IgM seric antibodies reactive with EHEC O157:H7, EHEC O111:H-, EPEC O111:H- and the levels of anti-LPS O111, LPS O157 and LPS O55 antibodies in healthy adults living in São Paulo, Brazil. The antibody levels were determined by an enzyme-linked immunosorbent assay for 100 individual serum samples, and the presence of anti-bacterial and anti-LPS seric antibodies was confirmed. Positive correlations were found among the three kinds of antibodies. The concentrations of IgM anti-LPS were significantly higher than those of IgG, and surprisingly, the concentrations of anti-LPS O157 were high in view of the infrequent isolation of O157 bacteria in Brazil. Our results suggest that there is a cross-reacting immunity to EHEC in the Brazilian population, which may be a result of the immunity to EPEC antigens. Alternatively, Brazilians may be exposed to EHEC more frequently than has previously been thought.
Assuntos
Anticorpos Antibacterianos/sangue , Diarreia/imunologia , Escherichia coli O157/imunologia , Escherichia coli/imunologia , Lipopolissacarídeos/imunologia , Adulto , Brasil , Reações Cruzadas , Diarreia/microbiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Estudos SoroepidemiológicosRESUMO
Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII) antibody (Ab) production are resistant or extremely susceptible to pristane-induced arthritis (PIA), respectively. Several quantitative trait loci regulating Ab production (Ab QTL) have been mapped in these lines, which were used to investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and their F1 and F2 intercrosses were injected twice with pristane, and arthritis was observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at day 105, while F1 and F2 mice showed intermediate values. HIII mice were totally resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100 alleles cosegregated significantly with PIA incidence, severity and onset in F2 intercross mice, while the other four markers showed suggestive values. Results indicate colocalization of QTL for Ab production and PIA susceptibility. Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes.
Assuntos
Artrite Experimental/genética , Artrite Experimental/imunologia , Autoanticorpos/biossíntese , Predisposição Genética para Doença , Locos de Características Quantitativas , Animais , Artrite Experimental/induzido quimicamente , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Terpenos/toxicidadeRESUMO
Mouse hepatitis virus 3 (MHV3) infection of A/J and BALB/c mice has been used as a model of resistance/susceptibility. A/J mice recover from a mild disease after 4-6 days of infection and the BALB/c mice develop an acute hepatitis and die after 3-4 days of infection. In view of studying the MHV3 binding to cells or cell extracts, we performed an enzyme-linked immunosorbent assay-like virus-binding assay, preparing microplates with L929 cells, A/J or BALB/c mouse macrophages and also with proteins extracted from these cells. Higher MHV3 bindings were observed to proteins of BALB/c macrophages than to the A/J ones. The interferon-gamma (IFN-gamma) activation led to a reduction of MHV3 binding only to proteins of resistant A/J mouse macrophages. Our experiments contribute to the hypothesis that IFN-gamma activation of macrophages plays an important role against MHV3 infection by downregulating the expression of viral receptors.
Assuntos
Infecções por Coronavirus/imunologia , Imunidade Inata , Macrófagos/imunologia , Vírus da Hepatite Murina/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , História do Século XX , Interferon gama/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB CRESUMO
IgY, the egg yolk immunoglobulin, equivalent to the IgG from mammals, has been used in veterinary practice for passive immunisation against bacterial or viral infectious diseases. Enteropathogenic Escherichia coli (EPEC) is the main etiological agent of infantile diarrhoea in Brazil and other developing countries. Our aims were to isolate immunoglobulin IgY from egg yolk laid by EPEC -immunised Leghorn chickens and to study its reactivity to the antigens from this pathogen, including some virulence factors. Leghorn chickens were immunised with a bacterial suspension intramuscularly (three hens) or intravenously (three hens) or with PBS (two hens). Eggs were collected over a period of 17 weeks. IgY isolation procedures were carried out by salt precipitation (ammonium sulphate, in solid form) followed by centrifugations and dialysis. Final preparations were submitted to sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS - PAGE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting. All immunised animals developed good levels of antibodies reactive to whole bacteria or lipopolysaccharide (LPS), in contrast to the control ones. Immunoblottings allowed the recognition of several antigenic fractions of bacterial antigens, some of which had a molecular weight compatible with bacterial virulence factors, confirming the efficacy of the immunisation and the adequacy of the method.
Assuntos
Galinhas/imunologia , Gema de Ovo/imunologia , Escherichia coli/imunologia , Imunoglobulinas/isolamento & purificação , Animais , Vacinas Bacterianas/imunologia , Galinhas/microbiologia , Gema de Ovo/microbiologia , Eletroforese em Gel de Poliacrilamida/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Feminino , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controleRESUMO
We reported seven cases (0.7%) of PTLD among 1002 renal transplants performed at Renal Transplant Service from Hospital São Paulo-Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil, between 1976 and 1997. There were three male and four female patients with median age of 37 year-old. According to Ann Arbor staging system there were four localized extra-nodal intermediate-grade NHL, one disseminated low-grade NHL and two polyclonal lymphoid hyperplasia. Four patients received cadaveric, two received related and one received unrelated renal transplant. PTLD occurred after a median latency period of 36 months (ranging from 5 to 84 months). In situ hybridization for EBER1 was performed in five patients and molecular evidence of EBV was found in 3 cases (two DLCL and one lymphoplasmocytoid lymphoma). All patients were treated with immunosuppression withdrawal, four patients received anthracyclin-based chemotherapy for control of localized or systemic clonal disease and three were treated with resection of primary PTLD. Four of seven patients (57%) are in complete remission 11, 20, 25 and 79 months after PTLD onset. One patient lost follow-up and two patients died due to lymphoma relapse, respectively 4 and 10 months after completion of treatment. In conclusion, our experience with this small group of patients showed that: 1) immunosuppression withdrawal is not necessarily associated with loss of renal transplant and can be used as the only treatment for polyclonal PTLD; 2) chemotherapy can simultaneously lead to clonal PTLD remission and periodic immunosuppression, avoiding graft rejection after immunosuppression withdrawal.
Assuntos
Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Brasil , Terapia Combinada , Gerenciamento Clínico , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/complicações , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/toxicidade , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/virologia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Resultado do TratamentoRESUMO
Together with the evidence that the reduced virus growth and the antiviral state induced by interferon (IFN)-gamma, occurring only in macrophages from resistant animals, correlated with the decrease of MHV3 binding to macrophage membrane proteins, we show here the expression of cellular and viral genes in resistant (A/J) and susceptible (BALB/c) mouse macrophages after IFN-gamma activation/infection. The expression of interferon response gene 47 and interferon regulatory factor 1 genes takes place after IFN-gamma activation in both macrophages, indicating their activation. The expression of the biliary glycoprotein 1(a) (Bgp1(a), the main virus receptor) decreased only in IFN-gamma-activated A/J mouse macrophages, in contrast to the expression of the Bgp2 (alternative receptor), which was not influenced by IFN-gamma activation. The synthesis of both viral mRNA and virus particles was delayed only in IFN-gamma-activated A/J mouse macrophages compared with susceptible BALB/c macrophages. Besides the evidence that IFN-gamma may modulate the expression of the Bgp1(a) isoform of carcinoembryonic antigen family, these data show that IFN-gamma, which induces resistance against MHV3 infection, may be involved in the down-regulation of the main viral receptor expression, a key step forward in our understanding of the molecular basis of resistance against virus infection.
Assuntos
Antivirais/imunologia , Regulação para Baixo , Glicoproteínas/metabolismo , Interferon gama/imunologia , Vírus da Hepatite Murina/imunologia , Receptores Virais/metabolismo , Animais , Antígenos CD , Antivirais/metabolismo , Moléculas de Adesão Celular , Células Cultivadas , Regulação Viral da Expressão Gênica , Genes Virais/genética , Glicoproteínas/genética , Interferon gama/metabolismo , Cinética , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Vírus da Hepatite Murina/genética , Vírus da Hepatite Murina/metabolismo , Vírus da Hepatite Murina/fisiologia , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Receptores Virais/genética , Replicação ViralRESUMO
The role of inflammatory and specific immune responses in pristane-induced arthritis (PIA) was investigated in mouse lines produced by bi-directional selective breedings for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reaction, comparing the outcome of PIA and the humoral and cellular response to hsp65. Symptoms of arthritis were detected in 50 % AIRmax mice 120 days after pristane injection, reaching a maximal incidence of 65 %, whereas only 7 % of AIRmin mice developed arthritis within an observation period of 200 days. The production of IgG antibody against hsp65 was found to be similar on both lines, although the IgG1 isotype was predominant in AIRmax, and IgG2a in AIRmin line. In vitro T cell proliferation to hsp65 was similar in the two lines, however, ELISPOT assays carried out soon after pristane treatment, demonstrated higher numbers of IL-6-, TNF-alpha- and IL-4-secreting cells in the spleen of AIRmax than in AIRmin mice, while higher numbers of IFN-gamma-producing cells were found in AIRmin mice. These results suggest a major participation of acute inflammatory mechanisms in the susceptibility to PIA. The genetic background which determines high or low AIR favors a Th2-like response in susceptible AIRmax and Th1-like response in resistant AIRmin mice at the initial phase of arthritis induction.
Assuntos
Artrite Reumatoide/imunologia , Inflamação/imunologia , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/fisiopatologia , Suscetibilidade a Doenças/imunologia , Imunossupressores/imunologia , Imunossupressores/toxicidade , Inflamação/fisiopatologia , Camundongos , Terpenos/imunologia , Terpenos/toxicidadeRESUMO
Host-parasite relationship and immunodiagnostic testing in paracoccidioidomycosis have been extensively investigated in recent years. We review the major advances in the understanding of pathogenesis of the disease with emphasis on the sequential steps in granuloma formation and the envolvement of immunological mechanisms in host defenses against the parasite. In addition, the several immunodiagnostic tests used for diagnosis and in the follow-up of patients are commented upon and critically analysed.
RESUMO
Confocal fluorescence microscopy combined with differential interference contrast imaging of tissues from chagasic patients enabled the unequivocal identification of the parasite Trypanosoma cruzi. Using different monoclonal antibodies that indicate the parasite form and replication stage in conjunction with DNA labelling, specimens derived from distinct clinical forms of the disease were examined. Intracellular amastigote forms of the parasite were clearly detected in heart, brain, skin, lung, and kidney. Dividing amastigotes as well as trypomastigote forms were recognized in samples obtained from patients undergoing either acute-phase or some form of reactivation caused by immunosuppression.
Assuntos
Anticorpos Monoclonais/imunologia , Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/parasitologia , Trypanosoma cruzi/isolamento & purificação , Adulto , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/análise , Encéfalo/parasitologia , Pré-Escolar , DNA de Protozoário/análise , Corantes Fluorescentes , Coração/parasitologia , Humanos , Indóis , Lactente , Fígado/parasitologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Pele/parasitologia , Trypanosoma cruzi/imunologiaRESUMO
Giardia duodenalis isolates from asymptomatic or symptomatic patients and from animals present similarities and differences in the protein composition, antigenic profile, pattern of proteases and isoenzymes, as well as in nucleic acids analysis. In the present overview, these differences and similarities are reviewed with emphasis in the host-parasite interplay and possible mechanisms of virulence of the protozoon.