RESUMO
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44- cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi-infected mice.
RESUMO
The Receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/Osteoprotegerine (OPG) system has been proposed as essential for osteoclast biology and identified as key part in regulating the physiology and pathology of the skeletal system. The study of the RANKL/RANK/OPG system has increased the understanding of the mechanisms involved in the bone remodeling process, especially in postmenopausal osteoporosis and periodontal disease. Bisphosphonates have become the mainstay of the treatment and prevention of post-menopausal osteoporosis. They inhibit the formation and dissolution of calcium phosphate crystals in bone and also osteoclasts, thus reducing bone turnover.Current investigations relate osteoporosis with the appearance and progression of periodontal disease. Although the etiology of both is different, the bone loss present in both shares several characteristics. Thus, therapy used for osteoporosis can be considered of value in the treatment of periodontal disease. The aim of this study was to evaluate the levels of RANKL, OPG and their relationship in gingival crevicular fluid (GCF) in patients with periodontal disease and postmenopausal osteoporosis/ osteopenia in relation to consumption of bisphosphonates. We studied 66 periodontal active sites obtained from 17 post- menopausal women patients aged between 45-70 years old with osteoporosis/osteopenia and periodontal disease. GCF samples were collected using sterile filter paper strips. To determine the concentration of RANKL and OPG, a commercial ELISA assay was used. The values of RANKL, OPG and their ratio (RANKL/ OPG) were compared with Mann-Whitney U Test. The values of RANKL, OPG and their ratio obtained in patients with osteoporosis/osteopenia and periodontal disease with or without bisphosphonates treatment showed no differences. Bisphosphonates do not alter the concentration of RANKL and OPG and their ratio in the GCF of patients with osteoporosis/ osteopenia and periodontal disease, probably because these cytokines may not be the main target of bisphosphonates to inhibit bone resorption in periodontal disease.
El sistema: Receptor activador del factor nuclear kappa-B ligando (RANKL)/RANK/Osteoprotegerina (OPG) ha sido propuestos como esencial para la biología osteoclástica, ya que ha sido identificado como participante clave en la regulación fisiológica y patológica del sistema óseo. El estudio del sistema RANKL-RANK-OPG ha facilitado la comprensión de los mecanismos intervinientes en el proceso de remodela- ción ósea, especialmente en la osteoporosis post-menopáusica y la enfermedad periodontal. Los bisfosfonatos se han convertido en el pilar principal del tratamiento y prevención de la osteoporosis post-menopáusica. Ellos inhiben la formación y disolución de los cristales de fosfato de calcio en el hueso y también inhiben a los osteoclastos reduciendo el recambio óseo. Actualmente, varios trabajos de investigación asocian la osteoporosis con el inicio y la progresión de la enfermedad periodontal. Aunque la etiología de ambas es diferente, la pérdida de masa ósea comparte varias características y la terapéutica utilizada para la osteoporosis puede ser considera de valor para el tratamiento de la enfermedad periodontal. El objetivo de este estudio fue evaluar el efecto del consumo de bifosfonatos en fluido crevicular (FC) sobre los niveles de RANKL, OPG y la relación RANKL/OPG en pacientes post-menopáusicas con enfermedad periodontal y osteoporosis/ osteopenia. Se estudiaron 66 sitios periodontalmente activos obtenidos de pacientes mujeres post-menopáusicas con edades entre 45-70 años de edad con enfermedad periodontal y osteoporosis/ osteopenia. La toma del FC se realizó mediante tiras de papel de filtro estériles. Para determinar la concentración de RANKL y OPG se utilizó el ensayo de ELISA comercial siguiendo las instrucciones del fabricante. Los valores obtenidos de las citoquinas y su relación fueron comparados con el Test U de Mann-Whitney. No se observaron diferencias en las concentraciones de RANKL y OPG encontradas, ni en su relación, en pacientes con enfermedad periodontal y osteoporosis/osteopenia con y sin tratamiento de bifosfonatos. Esto sugiere que probablemente estas citoquinas no serian el blanco principal de los bifosfonatos para inhibir la resorción ósea en la enfermedad periodontal.
Assuntos
Doenças Periodontais , Difosfonatos , Feminino , Líquido do Sulco Gengival , Humanos , Osteoporose Pós-Menopausa , OsteoprotegerinaRESUMO
El sistema receptor activador del factor nuclear kappa-B ligando (RANKL)/RANK/Osteoprotegerina (OPG) ha sido propuestos como esencial para la biología osteoclástica, yaque ha sido identificado como participante clave en la regulación fisiológica y patológica del sistema óseo. El estudio del sistema RANKL-RANK-OPG ha facilitado la comprensiónde los mecanismos intervinientes en el proceso de remodelación ósea, especialmente en la osteoporosis post-menopáusica y la enfermedad periodontal. Los bisfosfonatos se han convertido en el pilar principal deltratamiento y prevención de la osteoporosis post-menopáusica.Ellos inhiben la formación y disolución de los cristales de fosfato de calcio en el hueso y también inhiben a lososteoclastos reduciendo el recambio óseo. Actualmente, varios trabajos de investigación asocian la osteoporosis con el inicio y la progresión de la enfermedad periodontal. Aunque la etiología de ambas es diferente, lapérdida de masa ósea comparte varias características y la terapéutica utilizada para la osteoporosis puede serconsidera de valor para el tratamiento de la enfermedad periodontal. El objetivo de este estudio fue evaluar el efecto del consumo de bifosfonatos en fluido crevicular (FC) sobre los niveles de RANKL, OPG y la relación RANKL/OPG en pacientes post-menopáusicas con enfermedad periodontal y osteoporosis/ osteopenia.Se estudiaron 66 sitios periodontalmente activos obtenidos depacientes mujeres post-menopáusicas con edades entre 45-70 años de edad con enfermedad periodontal y osteoporosis/ osteopenia. La toma del FC se realizó mediante tiras de papel de filtro estériles. Para determinar la concentración de RANKL y OPG se utilizó el ensayo de ELISA comercial siguiendo las instrucciones delfabricante. Los valores obtenidos de las citoquinas y su relación fueron comparados con el Test U de Mann-Whitney...
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Difosfonatos/efeitos adversos , Doenças Periodontais/complicações , Ligante RANK , Osteoporose Pós-Menopausa/complicações , Osteoprotegerina , Receptor Ativador de Fator Nuclear kappa-B , Argentina , Ensaio de Imunoadsorção Enzimática/métodos , Líquido do Sulco Gengival , Perda do Osso Alveolar/etiologia , Estudos de Avaliação como Assunto , Interpretação Estatística de Dados , Faculdades de OdontologiaRESUMO
Here we identified B cells as a major source of rapid, innate-like production of interleukin 17 (IL-17) in vivo in response to infection with Trypanosoma cruzi. IL-17(+) B cells had a plasmablast phenotype, outnumbered cells of the TH17 subset of helper T cells and were required for an optimal response to this pathogen. With both mouse and human primary B cells, we found that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell-surface mucin CD45, which led to signaling dependent on the kinase Btk and production of IL-17A or IL-17F via a transcriptional program independent of the transcription factors RORγt and Ahr. Our combined data suggest that the generation of IL-17(+) B cells may be a previously unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.
Assuntos
Linfócitos B/imunologia , Doença de Chagas/imunologia , Glicoproteínas/metabolismo , Interleucina-17/imunologia , Neuraminidase/metabolismo , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/imunologia , Animais , Linfócitos B/parasitologia , Proliferação de Células , Células Cultivadas , Doença de Chagas/genética , Glicoproteínas/genética , Humanos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neuraminidase/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/parasitologia , Células Th17/imunologia , Células Th17/parasitologia , Ativação Transcricional/imunologiaRESUMO
Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils.
Assuntos
Doença de Chagas/imunologia , Neutrófilos/imunologia , Receptores de Interleucina-17/imunologia , Transdução de Sinais , Trypanosoma cruzi/imunologia , Animais , Células Cultivadas , Inflamação/imunologia , Interferon gama/imunologia , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-17/imunologia , Fígado/imunologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Baço/imunologia , Baço/metabolismoRESUMO
B1 cells produce most natural Abs in unimmunized mice and play a key role in the response to thymus-independent Ags and microbial infection. Enlargement of B1 cell number in mice is often associated with autoimmunity. However, the factors that control peripheral B1 cell survival remain poorly characterized. Mice lacking the inhibitory receptor FcγRIIb exhibit a massive expansion in peritoneal B1 cells, implicating this receptor in B1 cell homeostasis. In this study, we show that peritoneal B1 cells express the highest levels of FcγRIIb among B cell subsets and are highly susceptible to FcγRIIb-mediated apoptosis. B1 cells upregulate FcγRIIb in response to innate signals, including CpG, and the B cell homeostatic cytokine BAFF efficiently protects activated B1 cells from FcγRIIb-mediated apoptosis via receptor downregulation. BAFF-transgenic mice manifest an expansion of peritoneal B1 cells that express lower levels of FcγRIIb and exhibit reduced susceptibility to apoptosis. Whereas both peritoneal B1 cells from wild-type and BAFF-transgenic mice immunized with CpG exhibit an increase in FcγRIIb levels, this change is blunted in BAFF-transgenic animals. Our combined results demonstrate that FcγRIIb controls peritoneal B1 cell survival and this program can be modulated by the BAFF signaling axis.
Assuntos
Fator Ativador de Células B/fisiologia , Subpopulações de Linfócitos B/citologia , Subpopulações de Linfócitos B/imunologia , Receptores de IgG/fisiologia , Animais , Apoptose/genética , Apoptose/imunologia , Fator Ativador de Células B/biossíntese , Fator Ativador de Células B/deficiência , Subpopulações de Linfócitos B/metabolismo , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Células Cultivadas , Predisposição Genética para Doença/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Cavidade Peritoneal/citologia , Receptores de IgG/biossíntese , Receptores de IgG/deficiência , Transdução de Sinais/genética , Transdução de Sinais/imunologiaRESUMO
In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ) B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non related antigens. To protect themselves, the parasites have evolved unique ways to evade B cell immune responses inducing apoptosis of MZ and conventional mature B cells. As a consequence of the parasite induced-apoptosis, the early IgM response and an already establish humoral immunity are affected during the protozoan parasite infection. Moreover, some trypanosomatides trigger bone marrow immature B cell apoptosis, influencing the generation of new mature B cells. Simultaneously with their ability to release antibodies, B cells produce cytokines/quemokines that influence the characteristic of cellular immune response and consequently the progression of parasite infections.
RESUMO
In America, there are two species of Trypanosoma that can infect humans: Trypanosoma cruzi, which is responsible for Chagas disease and Trypanosoma rangeli, which is not pathogenic. We have developed a model of vaccination in mice with T. rangeli epimastigotes that protects against T. cruzi infection. The goal of this work was to study the pattern of specific immunoglobulins in the peritoneum (the site of infection) and in the sera of mice immunized with T. rangeli before and after challenge with T. cruzi. Additionally, we studied the effects triggered by antigen-antibodies binding and the levels of key cytokines involved in the humoral response, such as IL-4, IL-5 and IL-6. The immunization triggered the production of antibodies reactive with T. cruzi in peritoneal fluid (PF) and in serum, mainly IgG1 and, to a lesser magnitude, IgG2. Only immunized mice developed specific IgG3 antibodies in their peritoneal cavities. Antibodies were able to bind to the surface of the parasites and agglutinate them. Among the cytokines studied, IL-6 was elevated in PF during early infection, with higher levels in non-immunized-infected mice. The results indicate that T. rangeli vaccination against T. cruzi infection triggers a high production of specific IgG isotypes in PF and sera before infection and modulates the levels of IL-6 in PF in the early periods of infection.
Assuntos
Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Imunoglobulinas/imunologia , Interleucina-6/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma rangeli/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Testes de Hemaglutinação , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
In America, there are two species of Trypanosoma that can infect humans: Trypanosoma cruzi, which is responsible for Chagas disease and Trypanosoma rangeli, which is not pathogenic. We have developed a model of vaccination in mice with T. rangeli epimastigotes that protects against T. cruzi infection. The goal of this work was to study the pattern of specific immunoglobulins in the peritoneum (the site of infection) and in the sera of mice immunized with T. rangeli before and after challenge with T. cruzi. Additionally, we studied the effects triggered by antigen-antibodies binding and the levels of key cytokines involved in the humoral response, such as IL-4, IL-5 and IL-6. The immunization triggered the production of antibodies reactive with T. cruzi in peritoneal fluid (PF) and in serum, mainly IgG1 and, to a lesser magnitude, IgG2. Only immunized mice developed specific IgG3 antibodies in their peritoneal cavities. Antibodies were able to bind to the surface of the parasites and agglutinate them. Among the cytokines studied, IL-6 was elevated in PF during early infection, with higher levels in non-immunized-infected mice. The results indicate that T. rangeli vaccination against T. cruzi infection triggers a high production of specific IgG isotypes in PF and sera before infection and modulates the levels of IL-6 in PF in the early periods of infection.
Assuntos
Animais , Camundongos , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Imunoglobulinas/imunologia , /imunologia , Vacinas Protozoárias/imunologia , Trypanosoma rangeli/imunologia , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Testes de Hemaglutinação , Interleucinas/imunologia , Camundongos Endogâmicos BALB CRESUMO
Acute infection with Trypanosoma cruzi, the aetiological agent of Chagas' disease, results in parasitaemia and polyclonal lymphocyte activation. It has been reported that polyclonal B-cell activation is associated with hypergammaglobulinaemia and delayed parasite-specific antibody response. In the present study we analysed the development of a B-cell response within the different microenvironments of the spleen during acute T. cruzi infection. We observed massive germinal centre (GC) and extrafollicular (EF) responses at the peak of infection. However, the EF foci were evident since day 3 post-infection (p.i.), and, early in the infection, they mainly provided IgM. The EF foci response reached its peak at 11 days p.i. and extended from the red pulp into the periarteriolar lymphatic sheath. The GCs were detected from day 8 p.i. At the peak of parasitaemia, CD138(+) B220(+) plasma cells in EF foci, red pulp and T-cell zone expressed IgM and all the IgG isotypes. Instead of the substantial B-cell response, most of the antibodies produced by splenic cells did not target the parasite, and parasite-specific IgG isotypes could be detected in sera only after 18 days p.i. We also observed that the bone marrow of infected mice presented a strong reduction in CD138(+) B220(+) cells compared with that of normal mice. Hence, in acute infection with T. cruzi, the spleen appears to be the most important lymphoid organ that lodges plasma cells and the main producer of antibodies. The development of a B-cell response during T. cruzi infection shows features that are particular to T. cruzi and other protozoan infection but different to other infections or immunization with model antigens.
Assuntos
Anticorpos/imunologia , Linfócitos B/imunologia , Baço/citologia , Baço/imunologia , Trypanosoma cruzi/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
BACKGROUND: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.
Assuntos
Anticorpos Antiprotozoários/biossíntese , Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Doença de Chagas/imunologia , Baço/imunologia , Trypanosoma cruzi/imunologia , Animais , Fator Ativador de Células B/antagonistas & inibidores , Modelos Animais de Doenças , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Humoral immunity during experimental Chagas disease has been considered a double-edge sword, critical to control Trypanosoma cruzi spreading but also associated to tissue damage. Peritoneal B-1 cells have been linked to the pathogenesis of Chagas disease; however, they may also help to control the infection by providing a fast wave of antibodies. In the present work, we determined that peritoneal B-cell response to T. cruzi is characterized by a marked reduction of CD19(+) B cells due to plasma cell differentiation rather than to cell death. Both peritoneal B-2 and B-1 cells decrease after parasite infection, but with different kinetics. Thus, the reduction in B-2 cell number can be detected from day 4 postinfection while the number of B-1 cells decreases only after 15 days of infection. Differentiation of peritoneal B-1 and B-2 cells into IgM-secreting cells was triggered by parasites but not by cytokines produced by peritoneal cells. Electron microscopy studies showed that peritoneum of infected mice lodges plasma cells with typical morphology as well as atypical plasma cells named 'Mott-like cells' containing high number of cytoplasmatic Ig(+) granules. The plasma cells induced during the infection showed a phenotype that may allow their persistence in peritoneum and they may contribute to the high levels of antibodies exhibited at the chronic phase of infection. We also showed that the peritoneal B-cell response is scarcely specific for the invading pathogen and rather constitute an important source of non-parasite-specific IgM and IgG in the infected host.
Assuntos
Anticorpos/imunologia , Doença de Chagas/imunologia , Peritônio/citologia , Peritônio/imunologia , Plasmócitos/citologia , Plasmócitos/imunologia , Trypanosoma cruzi/imunologia , Animais , Antígenos CD19/imunologia , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Plasmócitos/metabolismo , Sindecana-1/análise , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Polyclonal B cell activation is not a peculiar characteristic to a particular infection, as many viruses, bacteria, and parasites induce a strong polyclonal B cell response resulting in hyper-gamma-globulinemia. Here, we discuss the different roles proposed for polyclonal B cell activation, which can be crucial for early host defense against rapidly dividing microorganisms by contributing antibodies specific for a spectrum of conserved structures present in the pathogens. In addition, polyclonal B cell activation can be responsible for maintenance of memory B cell responses because of the continuous, unrestricted stimulation of memory B cells whose antibody production may be sustained in the absence of the antigens binding-specific BCR. Conversely, polyclonal activation can be triggered by microorganisms to avoid the host-specific, immune response by activating B cell clones, which produce nonmicroorganism-specific antibodies. Finally, some reports suggest a deleterious role for polyclonal activation, arguing that it could potentially turn on anti-self-responses and lead to autoimmune manifestations during chronic infections.
Assuntos
Doenças Autoimunes/etiologia , Autoimunidade , Linfócitos B/imunologia , Infecções/imunologia , Animais , Humanos , Memória Imunológica , Ativação LinfocitáriaRESUMO
El objetivo general de este proyecto fue estudiar la participación de Baff y CD40L en la activación, diferenciación y sobrevida de linfocitos B de zona marginal y su contribución a la inmunopatología en la enfermedad de Chagas. Para llevar a cabo los objetivos propuestos, se utilizaron ratones hembras de la cepa Balb/c de 6 a 8 semanas, las cuales fueron infectadas con una dosis de 500 tripomastigotes de T. cruzi de la cepa Tulahuén /animal/200 ul de PBS. Ratones normales inyectados con 200 ul de PBS fueron utilizados como controles. Es importante señalar que los cambios producidos en las distintas poblaciones celulares, determinadas por citometria de flujo, recién fueron evidentes a varios días después de la infección, Por lo tanto es posible que las modificaciones observadas en la población de LiB de ZM en los animales con pocas horas de infección, se debe a que CD40L sea aportado por alguna población no presente en bazo o presente en el mismo y que no hemos determinado. También es posible que en las primeras horas de infección no se produzca un cambio numérico en población celular, pero que la población se active y secrete CD40L o Baff
Assuntos
Doença de Chagas , Linfócitos B , Bolsas de EstudoRESUMO
El objetivo general de este proyecto fue estudiar la participación de Baff y CD40L en la activación, diferenciación y sobrevida de linfocitos B de zona marginal y su contribución a la inmunopatología en la enfermedad de Chagas. Para llevar a cabo los objetivos propuestos, se utilizaron ratones hembras de la cepa Balb/c de 6 a 8 semanas, las cuales fueron infectadas con una dosis de 500 tripomastigotes de T. cruzi de la cepa Tulahuén /animal/200 ul de PBS. Ratones normales inyectados con 200 ul de PBS fueron utilizados como controles. Es importante señalar que los cambios producidos en las distintas poblaciones celulares, determinadas por citometria de flujo, recién fueron evidentes a varios días después de la infección, Por lo tanto es posible que las modificaciones observadas en la población de LiB de ZM en los animales con pocas horas de infección, se debe a que CD40L sea aportado por alguna población no presente en bazo o presente en el mismo y que no hemos determinado. También es posible que en las primeras horas de infección no se produzca un cambio numérico en población celular, pero que la población se active y secrete CD40L o Baff
Assuntos
Doença de Chagas , Linfócitos B , Bolsas de EstudoRESUMO
El objetivo general de este proyecto fue estudiar la participación de Baff y CD40L en la activación, diferenciación y sobrevida de linfocitos B de zona marginal y su contribución a la inmunopatología en la enfermedad de Chagas. Para llevar a cabo los objetivos propuestos, se utilizaron ratones hembras de la cepa Balb/c de 6 a 8 semanas, las cuales fueron infectadas con una dosis de 500 tripomastigotes de T. cruzi de la cepa Tulahuén /animal/200 ul de PBS. Ratones normales inyectados con 200 ul de PBS fueron utilizados como controles. Es importante señalar que los cambios producidos en las distintas poblaciones celulares, determinadas por citometria de flujo, recién fueron evidentes a varios días después de la infección, Por lo tanto es posible que las modificaciones observadas en la población de LiB de ZM en los animales con pocas horas de infección, se debe a que CD40L sea aportado por alguna población no presente en bazo o presente en el mismo y que no hemos determinado. También es posible que en las primeras horas de infección no se produzca un cambio numérico en población celular, pero que la población se active y secrete CD40L o Baff