Belen De Andres - Academia.edu (original) (raw)

Papers by Belen De Andres

The Journal of pathology, Jan 4, 2017

Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progres... more Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. However, the effects of hemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway and altered podocyte morphology, with decreased expressionof the slit diaphragm proteins nephrin and synaptopodin. Hb-uptake activated the nuclear factor erythroid-2-related factor 2 (Nrf2) and induced expression of the Nrf2-related antioxidant proteins HO-1 and ferritin. Nrf2 activation and Hb staining was observed in podocytes of mice with intravascular hemolysis. These mice developed proteinuria and showed podocyte injury, characterized by foot process effacement, decreased s...

PLoS pathogens, 2016

Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such... more Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium -the amidase LytA- were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination fr...

Cellular Microbiology, 2015

Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are f... more Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are fungal cells of abnormal enlarged size. Little is known about the factors that trigger titan cells. In particular, it is not known how the host environment influences this transition. In this work, we describe the formation of titan cells in two mouse strains, CD1 and C57BL/6J. We found that the proportion of C. neoformans titan cells was significantly higher in C57BL/6J mice than in CD1. This higher proportion of titan cells was associated with a higher dissemination of the yeasts to the brain. Histology sections demonstrated eosinophilia in infected animals, although it was significantly lower in the CD1 mice which presented infiltration of lymphocytes. Both mouse strains presented infiltration of granulocytes, but the amount of eosinophils was higher in C57BL/6J. CD1 mice showed a significant accumulation of IFN-γ, TNF-α and IL17, while C57BL/BL mice had an increase in the anti-inflammatory cytokine IL-4. IgM antibodies to the polysaccharide capsule and total IgE were more abundant in the sera from C57BL/6J, confirming that these animals present a Th2-type response. We conclude that titan cell formation in C. neoformans depends, not only on microbe factors, but also on the host environment.

Glia, 2015

DNGR-1+ dendritic cells are located in meningeal membrane and choroid plexus of the non-injured b... more DNGR-1+ dendritic cells are located in meningeal membrane and choroid plexus of the non-injured brain.

European Journal of Immunology, 2015

Journal of Clinical Investigation, 2003

Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagi... more Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagination that reacts to factor signaling from both cardiac mesoderm and septum transversum mesenchyme. Current knowledge of the progenitor stem cell populations involved in this early embryo liver development is scarce. We describe here a population of 11-day postcoitus c-Kit low (CD45/TER119)liver progenitors that selectively expressed hepatospecific genes and proteins in vivo, was self-maintained in vitro by longterm proliferation, and simultaneously differentiated into functional hepatocytes and bile duct cells. Purified c-Kit low (CD45/TER119)liver cells cocultured with cell-depleted fetal liver fragments engrafted and repopulated the hepatic cell compartments of the latter organoids, suggesting that they may include the embryonic stem cells responsible for liver development.

The Journal of Immunology

Sézary syndrome (SS) is a leukemic form of cutaneous mature T-cell lymphoma characterized by circ... more Sézary syndrome (SS) is a leukemic form of cutaneous mature T-cell lymphoma characterized by circulating malignant CD4 T lymphocytes (Sezary cells). Patients with SS have a poor prognosis and current treatment options show high rates of relapse, morbidity or mortality. Thus, there is an unmet need for an efficient and safe treatment. Sézary cells have unique clonal potentially targetable epitopes, including their TCR, and TCR- and neoantigen-derived HLA-restricted peptides. Our general aim is to design a patient-tailored two-pronged strategy against SS. The specific aims are 1) to target SS clonal TCR B cell epitopes using mAb and/or CAR T cells, 2) to target SS HLA-restricted T-cell epitopes using TCR peptide- and/or neoantigen-specific human T cells, and 3) to validate efficacy in vitro and in mouse models. For the generation of mAb, apheresis-purified SS cells or SS TCR CDR3beta peptides were used for immunizations, and screening was done on SS vs non-SS CD4 cells as defined by f...

The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an... more The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant V γ4/Vδ1 TCR. The apparent lack of other γδ TCR species suggests that a selection mechanism might operate to regulate the localization of γδ T cells at this anatomical site. Selection might be connected to the V γ4/Vδ1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17–18 of embryonic life. In the present studies, we investigated whether transgenic γδ cells expressing a TCR species characteristic of the subpopulation of γδ T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic V γ2 TCRF cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal γδ T cells, the transgenic vaginal γδ T cells expressed the phenotype of recently activated memory/effector T cells (CD44 hi, CD62L–, CD45RBlo, CD69F). Vaginal γδ T cells in normal mice do not express the CD2...

El sistema inmunitario es capaz de recordar y generar mejores respuestas tras el primer encuentro... more El sistema inmunitario es capaz de recordar y generar mejores respuestas tras el primer encuentro con un patógeno que le infecta, de manera que posteriormente pueda combatirlo mejor. Esto permite el uso de las vacunas, que utilizan derivados de microorganismos (muertos, debilitados o fragmentos antigénicos derivados de ellos) y que, al administrarse a personas sanas susceptibles a la enfermedad, inducen una RI de memoria protectora que eliminará eficazmente las sucesivas invasiones del mismo agente infeccioso, sin provocar síntomas de infección. Sin embargo, a veces las respuestas que se obtienen tras una inmunización no son tan eficientes como las obtenidas tras la infección real, por lo que se necesitaría repetir la inmunización varias veces, mediante la administración de dosis de recuerdo, para obtener respuestas protectoras.Capítulo 1. La epopeya de la viruela como ejemplo del éxito de las vacunas. Capítulo 2. El sistema de defensa de nuestro cuerpo. Capítulo 3. La respuesta inmunitaria frente a la infección por patógenos. Capítulo 4. Tipos de vacunas. Capítulo 5. Nuevas tecnologías en el desarrollo o mejora de vacunas. Capítulo 6. Vacunación a lo largo de la vida: de la infancia a la vejez. Capítulo 7. Vacunas recomendadas en las diferentes etapas de la vida. Capítulo 8. Seguridad de las vacunas. Mitos y errores sobre vacunación. Capítulo 9. ¿por qué es necesario seguir vacunando?. Capítulo 10. Cuánto nos ahorramos al vacunarnos. Capítulo 11. Efectos beneficiosos añadidos de las vacunas: el caso del sarampión. Capítulo 12. Las vacunas nos protegen a todos, incluso a los no vacunados. Capítulo 13. Enfermedades para las que se necesitan con urgencia planes globales de vacunación. Capítulo 14. Nuevas vacunas sostenibles para los países en desarrollo. Glosario. Bibliografía

Frontiers in Immunology, 2020

Streptococcus pneumoniae is the main cause of bacterial pneumonia, a condition that currently pro... more Streptococcus pneumoniae is the main cause of bacterial pneumonia, a condition that currently produces significant global morbidity and mortality. The initial immune response to this bacterium occurs when the innate system recognizes common motifs expressed by many pathogens, events driven by pattern recognition receptors like the Toll-like family receptors (TLRs). In this study, lung myeloid-cell populations responsible for the innate immune response (IIR) against S. pneumoniae, and their dependence on the TLR4-signaling axis, were analyzed in TLR4 −/− and Myeloid-Differentiation factor-88 deficient (MyD88 −/−) mice. Neutrophils and monocyte-derived cells were recruited in infected mice 3-days post-infection. Compared to wild-type mice, there was an increased bacterial load in both these deficient mouse strains and an altered IIR, although TLR4 −/− mice were more susceptible to bacterial infection. These mice also developed fewer alveolar macrophages, weaker neutrophil infiltration, less Ly6C high monocyte differentiation and a disrupted classical and non-classical monocyte profile. The pro-inflammatory cytokine profile (CXCL1, TNF-α, IL-6, and IL-1β) was also severely affected by the lack of TLR4 and no induction of Th1 was observed in these mice. The respiratory burst (ROS production) after infection was profoundly dampened in TLR4 −/− and MyD88 −/− mice. These data demonstrate the complex dynamics of myeloid populations and a key role of the TLR4-signaling axis in the IIR to S. pneumoniae, which involves both the MyD88 and TRIF (Toll/IL-1R domain-containing adaptor-inducing IFN-β) dependent pathways.

Blood, 1997

Murine granulocytes and precursors express low-affinity IgG Fc receptors (FcγR). We investigated ... more Murine granulocytes and precursors express low-affinity IgG Fc receptors (FcγR). We investigated the effects of FcγR ligation on the development of eosinophils in cultures of normal murine bone marrow. Eosinophilopoiesis was induced by culture of bone marrow cells in the presence of cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-3 [IL-3], and IL-5). Addition to the cultures of 2.4G2, a rat monoclonal antibody (mAb) that reacts with FcγRII (CD32) and FcγRIII (CD16), induced granulocyte apoptosis within 24 hours. Granulocytes in cultures that contained 2.4G2 showed chromatin condensation, binding of Annexin-V, and fas induction, and by electron microscopy, apoptosis was most commonly observed in cells of the eosinophil lineage. Since murine granulocytes can express both FcγRII (CD32) and FcγRIII (CD16), we investigated the effect of 2.4G2 on cultures of bone marrow obtained from FcγRIII (CD16) gene–disrupted mice and found that the apoptosis induced ...

Blood, 1998

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (... more Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcγR) designated as FcγRII (CD32) and FcγRIII (CD16), but mature B lymphocytes only express FcγRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcγR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220+, sIgM−, HSAhigh, FcγR+) from normal bone marrow were cocultured with BM...

Cell Death & Disease, 2017

Aging has a strong impact on the activity of the immune system, enhancing susceptibility to patho... more Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19+CD45R+CD21++CD23lo) and a decrease of naive B cells (CD19+IgD+), whereas there is an enhancement of a CD19+CD45Rlo innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R+CD21loCD23loCD5−CD11b−) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (VH) diversity, with a diminution on IgG1-memory B cells (CD11b−Gr1−CD138−IgM−IgD−CD19+CD38+IgG1+), an increase in T follicular helper (TFH, CD4+CXCR5+PD1+) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band ...

Journal of Visualized Experiments, 2016

PLOS ONE, 2016

We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory altera... more We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory alterations in rat kidney by aldosterone + salt administration. The effects of treatment with spironolactone on above parameters were also analyzed. Male Wistar rats received aldosterone (1 mgkg-1 d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg kg-1 d-1). Systolic and diastolic blood pressures were elevated (p<0.05) in aldosterone + salt-treated rats. Relative kidney weight, collagen content, fibronectin, macrophage infiltrate, CTGF, Col I, MMP2, TNF-α, CD68, Arg2, and SGK-1 were increased (p<0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (p<0.05). Increased iNOS and IFN-γ mRNA gene expression (M1 macrophage markers) was observed in aldosterone + salt rats, whereas no significant differences were observed in IL-10 and gene ArgI mRNA expression or ED2 protein content (M2 macrophage markers). All the observed changes were blocked with spironolactone treatment. Macrophage depletion with liposomal clodronate reduced macrophage influx and inflammatory M1 markers (INF-γ or iNOS), whereas interstitial fibrosis was only partially reduced after this intervention, in aldosterone plus salt-treated rats. In conclusion, aldosterone + salt administration mediates inflammatory M1 macrophage phenotype and increased fibrosis throughout mineralocorticoid receptors activation.

Blood, Jan 15, 1998

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (... more Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcgammaR) designated as FcgammaRII (CD32) and FcgammaRIII (CD16), but mature B lymphocytes only express FcgammaRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcgammaR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220(+), sIgM-, HSAhigh, FcgammaR+) from normal bone marr...

words Manuscript: 5476 words SCIENTIFIC SECTION HEADING : Immunobiology

The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused... more The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused by the ingestion of rapeseed oil denatured with 2% aniline. Due to the clinical course of the disease, immunopathological mechanisms have been suspected but a direct connection was never demonstrated. To analyse this possibility, we determined several immunological parameters in the sera of patients with TOS and without the disease, using a case-control design: total immunoglobulins, IgG and IgE antibodies against different toxic agents (oleylanilide, aniline, linoleyl-anilide, and 3-phenylaminopropane-1-2-diol), autoantibodies, cytokines (IL-4, IL-6, TNF, GM-CSF) and soluble receptors (sCD23 and sIL-2R). We detected high levels of sIL-2R in TOS patients compared to controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). A higher levels of sCD23 and IgE were also found. In addition, the response to oleyl-anilide of peripheral blood lymphocytes from TOS patients was studied and a significant proliferative response in 30% of TOS patients versus 5% controls was observed. Our data support the implication of the immune system in the acute phase of TOS, with a possible activation of T-cells and release of cytokines, that could explain some of the clinical findings in this phase of the disease.

The Journal of pathology, Jan 4, 2017

Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progres... more Recurrent and massive intravascular hemolysis induces proteinuria, glomerulosclerosis and progressive impairment of renal function, suggesting podocyte injury. However, the effects of hemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin-cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway and altered podocyte morphology, with decreased expressionof the slit diaphragm proteins nephrin and synaptopodin. Hb-uptake activated the nuclear factor erythroid-2-related factor 2 (Nrf2) and induced expression of the Nrf2-related antioxidant proteins HO-1 and ferritin. Nrf2 activation and Hb staining was observed in podocytes of mice with intravascular hemolysis. These mice developed proteinuria and showed podocyte injury, characterized by foot process effacement, decreased s...

PLoS pathogens, 2016

Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such... more Bacterial uptake by phagocytic cells is a vital event in the clearance of invading pathogens such as Streptococcus pneumoniae. A major role of the P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes against invasive pneumococcal disease is described in this study. Phagocytosis experiments using different serotypes demonstrated that PSGL-1 is involved in the recognition, uptake and killing of S. pneumoniae. Co-localization of several clinical isolates of S. pneumoniae with PSGL-1 was demonstrated, observing a rapid and active phagocytosis in the presence of PSGL-1. Furthermore, the pneumococcal capsular polysaccharide and the main autolysin of the bacterium -the amidase LytA- were identified as bacterial ligands for PSGL-1. Experimental models of pneumococcal disease including invasive pneumonia and systemic infection showed that bacterial levels were markedly increased in the blood of PSGL-1-/- mice. During pneumonia, PSGL-1 controls the severity of pneumococcal dissemination fr...

Cellular Microbiology, 2015

Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are f... more Cryptococcus neoformans is a pathogenic yeast that can form titan cells in the lungs, which are fungal cells of abnormal enlarged size. Little is known about the factors that trigger titan cells. In particular, it is not known how the host environment influences this transition. In this work, we describe the formation of titan cells in two mouse strains, CD1 and C57BL/6J. We found that the proportion of C. neoformans titan cells was significantly higher in C57BL/6J mice than in CD1. This higher proportion of titan cells was associated with a higher dissemination of the yeasts to the brain. Histology sections demonstrated eosinophilia in infected animals, although it was significantly lower in the CD1 mice which presented infiltration of lymphocytes. Both mouse strains presented infiltration of granulocytes, but the amount of eosinophils was higher in C57BL/6J. CD1 mice showed a significant accumulation of IFN-γ, TNF-α and IL17, while C57BL/BL mice had an increase in the anti-inflammatory cytokine IL-4. IgM antibodies to the polysaccharide capsule and total IgE were more abundant in the sera from C57BL/6J, confirming that these animals present a Th2-type response. We conclude that titan cell formation in C. neoformans depends, not only on microbe factors, but also on the host environment.

Glia, 2015

DNGR-1+ dendritic cells are located in meningeal membrane and choroid plexus of the non-injured b... more DNGR-1+ dendritic cells are located in meningeal membrane and choroid plexus of the non-injured brain.

European Journal of Immunology, 2015

Journal of Clinical Investigation, 2003

Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagi... more Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagination that reacts to factor signaling from both cardiac mesoderm and septum transversum mesenchyme. Current knowledge of the progenitor stem cell populations involved in this early embryo liver development is scarce. We describe here a population of 11-day postcoitus c-Kit low (CD45/TER119)liver progenitors that selectively expressed hepatospecific genes and proteins in vivo, was self-maintained in vitro by longterm proliferation, and simultaneously differentiated into functional hepatocytes and bile duct cells. Purified c-Kit low (CD45/TER119)liver cells cocultured with cell-depleted fetal liver fragments engrafted and repopulated the hepatic cell compartments of the latter organoids, suggesting that they may include the embryonic stem cells responsible for liver development.

The Journal of Immunology

Sézary syndrome (SS) is a leukemic form of cutaneous mature T-cell lymphoma characterized by circ... more Sézary syndrome (SS) is a leukemic form of cutaneous mature T-cell lymphoma characterized by circulating malignant CD4 T lymphocytes (Sezary cells). Patients with SS have a poor prognosis and current treatment options show high rates of relapse, morbidity or mortality. Thus, there is an unmet need for an efficient and safe treatment. Sézary cells have unique clonal potentially targetable epitopes, including their TCR, and TCR- and neoantigen-derived HLA-restricted peptides. Our general aim is to design a patient-tailored two-pronged strategy against SS. The specific aims are 1) to target SS clonal TCR B cell epitopes using mAb and/or CAR T cells, 2) to target SS HLA-restricted T-cell epitopes using TCR peptide- and/or neoantigen-specific human T cells, and 3) to validate efficacy in vitro and in mouse models. For the generation of mAb, apheresis-purified SS cells or SS TCR CDR3beta peptides were used for immunizations, and screening was done on SS vs non-SS CD4 cells as defined by f...

The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an... more The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant V γ4/Vδ1 TCR. The apparent lack of other γδ TCR species suggests that a selection mechanism might operate to regulate the localization of γδ T cells at this anatomical site. Selection might be connected to the V γ4/Vδ1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17–18 of embryonic life. In the present studies, we investigated whether transgenic γδ cells expressing a TCR species characteristic of the subpopulation of γδ T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic V γ2 TCRF cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal γδ T cells, the transgenic vaginal γδ T cells expressed the phenotype of recently activated memory/effector T cells (CD44 hi, CD62L–, CD45RBlo, CD69F). Vaginal γδ T cells in normal mice do not express the CD2...

El sistema inmunitario es capaz de recordar y generar mejores respuestas tras el primer encuentro... more El sistema inmunitario es capaz de recordar y generar mejores respuestas tras el primer encuentro con un patógeno que le infecta, de manera que posteriormente pueda combatirlo mejor. Esto permite el uso de las vacunas, que utilizan derivados de microorganismos (muertos, debilitados o fragmentos antigénicos derivados de ellos) y que, al administrarse a personas sanas susceptibles a la enfermedad, inducen una RI de memoria protectora que eliminará eficazmente las sucesivas invasiones del mismo agente infeccioso, sin provocar síntomas de infección. Sin embargo, a veces las respuestas que se obtienen tras una inmunización no son tan eficientes como las obtenidas tras la infección real, por lo que se necesitaría repetir la inmunización varias veces, mediante la administración de dosis de recuerdo, para obtener respuestas protectoras.Capítulo 1. La epopeya de la viruela como ejemplo del éxito de las vacunas. Capítulo 2. El sistema de defensa de nuestro cuerpo. Capítulo 3. La respuesta inmunitaria frente a la infección por patógenos. Capítulo 4. Tipos de vacunas. Capítulo 5. Nuevas tecnologías en el desarrollo o mejora de vacunas. Capítulo 6. Vacunación a lo largo de la vida: de la infancia a la vejez. Capítulo 7. Vacunas recomendadas en las diferentes etapas de la vida. Capítulo 8. Seguridad de las vacunas. Mitos y errores sobre vacunación. Capítulo 9. ¿por qué es necesario seguir vacunando?. Capítulo 10. Cuánto nos ahorramos al vacunarnos. Capítulo 11. Efectos beneficiosos añadidos de las vacunas: el caso del sarampión. Capítulo 12. Las vacunas nos protegen a todos, incluso a los no vacunados. Capítulo 13. Enfermedades para las que se necesitan con urgencia planes globales de vacunación. Capítulo 14. Nuevas vacunas sostenibles para los países en desarrollo. Glosario. Bibliografía

Frontiers in Immunology, 2020

Streptococcus pneumoniae is the main cause of bacterial pneumonia, a condition that currently pro... more Streptococcus pneumoniae is the main cause of bacterial pneumonia, a condition that currently produces significant global morbidity and mortality. The initial immune response to this bacterium occurs when the innate system recognizes common motifs expressed by many pathogens, events driven by pattern recognition receptors like the Toll-like family receptors (TLRs). In this study, lung myeloid-cell populations responsible for the innate immune response (IIR) against S. pneumoniae, and their dependence on the TLR4-signaling axis, were analyzed in TLR4 −/− and Myeloid-Differentiation factor-88 deficient (MyD88 −/−) mice. Neutrophils and monocyte-derived cells were recruited in infected mice 3-days post-infection. Compared to wild-type mice, there was an increased bacterial load in both these deficient mouse strains and an altered IIR, although TLR4 −/− mice were more susceptible to bacterial infection. These mice also developed fewer alveolar macrophages, weaker neutrophil infiltration, less Ly6C high monocyte differentiation and a disrupted classical and non-classical monocyte profile. The pro-inflammatory cytokine profile (CXCL1, TNF-α, IL-6, and IL-1β) was also severely affected by the lack of TLR4 and no induction of Th1 was observed in these mice. The respiratory burst (ROS production) after infection was profoundly dampened in TLR4 −/− and MyD88 −/− mice. These data demonstrate the complex dynamics of myeloid populations and a key role of the TLR4-signaling axis in the IIR to S. pneumoniae, which involves both the MyD88 and TRIF (Toll/IL-1R domain-containing adaptor-inducing IFN-β) dependent pathways.

Blood, 1997

Murine granulocytes and precursors express low-affinity IgG Fc receptors (FcγR). We investigated ... more Murine granulocytes and precursors express low-affinity IgG Fc receptors (FcγR). We investigated the effects of FcγR ligation on the development of eosinophils in cultures of normal murine bone marrow. Eosinophilopoiesis was induced by culture of bone marrow cells in the presence of cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-3 [IL-3], and IL-5). Addition to the cultures of 2.4G2, a rat monoclonal antibody (mAb) that reacts with FcγRII (CD32) and FcγRIII (CD16), induced granulocyte apoptosis within 24 hours. Granulocytes in cultures that contained 2.4G2 showed chromatin condensation, binding of Annexin-V, and fas induction, and by electron microscopy, apoptosis was most commonly observed in cells of the eosinophil lineage. Since murine granulocytes can express both FcγRII (CD32) and FcγRIII (CD16), we investigated the effect of 2.4G2 on cultures of bone marrow obtained from FcγRIII (CD16) gene–disrupted mice and found that the apoptosis induced ...

Blood, 1998

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (... more Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcγR) designated as FcγRII (CD32) and FcγRIII (CD16), but mature B lymphocytes only express FcγRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcγR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220+, sIgM−, HSAhigh, FcγR+) from normal bone marrow were cocultured with BM...

Cell Death & Disease, 2017

Aging has a strong impact on the activity of the immune system, enhancing susceptibility to patho... more Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19+CD45R+CD21++CD23lo) and a decrease of naive B cells (CD19+IgD+), whereas there is an enhancement of a CD19+CD45Rlo innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R+CD21loCD23loCD5−CD11b−) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (VH) diversity, with a diminution on IgG1-memory B cells (CD11b−Gr1−CD138−IgM−IgD−CD19+CD38+IgG1+), an increase in T follicular helper (TFH, CD4+CXCR5+PD1+) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band ...

Journal of Visualized Experiments, 2016

PLOS ONE, 2016

We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory altera... more We aimed to evaluate macrophages heterogeneity and structural, functional and inflammatory alterations in rat kidney by aldosterone + salt administration. The effects of treatment with spironolactone on above parameters were also analyzed. Male Wistar rats received aldosterone (1 mgkg-1 d-1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg kg-1 d-1). Systolic and diastolic blood pressures were elevated (p<0.05) in aldosterone + salt-treated rats. Relative kidney weight, collagen content, fibronectin, macrophage infiltrate, CTGF, Col I, MMP2, TNF-α, CD68, Arg2, and SGK-1 were increased (p<0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (p<0.05). Increased iNOS and IFN-γ mRNA gene expression (M1 macrophage markers) was observed in aldosterone + salt rats, whereas no significant differences were observed in IL-10 and gene ArgI mRNA expression or ED2 protein content (M2 macrophage markers). All the observed changes were blocked with spironolactone treatment. Macrophage depletion with liposomal clodronate reduced macrophage influx and inflammatory M1 markers (INF-γ or iNOS), whereas interstitial fibrosis was only partially reduced after this intervention, in aldosterone plus salt-treated rats. In conclusion, aldosterone + salt administration mediates inflammatory M1 macrophage phenotype and increased fibrosis throughout mineralocorticoid receptors activation.

Blood, Jan 15, 1998

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (... more Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcgammaR) designated as FcgammaRII (CD32) and FcgammaRIII (CD16), but mature B lymphocytes only express FcgammaRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcgammaR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220(+), sIgM-, HSAhigh, FcgammaR+) from normal bone marr...

words Manuscript: 5476 words SCIENTIFIC SECTION HEADING : Immunobiology

The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused... more The toxic oil syndrome (TOS), a multisystemic disease, that occurred in Spain in 1981, was caused by the ingestion of rapeseed oil denatured with 2% aniline. Due to the clinical course of the disease, immunopathological mechanisms have been suspected but a direct connection was never demonstrated. To analyse this possibility, we determined several immunological parameters in the sera of patients with TOS and without the disease, using a case-control design: total immunoglobulins, IgG and IgE antibodies against different toxic agents (oleylanilide, aniline, linoleyl-anilide, and 3-phenylaminopropane-1-2-diol), autoantibodies, cytokines (IL-4, IL-6, TNF, GM-CSF) and soluble receptors (sCD23 and sIL-2R). We detected high levels of sIL-2R in TOS patients compared to controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). A higher levels of sCD23 and IgE were also found. In addition, the response to oleyl-anilide of peripheral blood lymphocytes from TOS patients was studied and a significant proliferative response in 30% of TOS patients versus 5% controls was observed. Our data support the implication of the immune system in the acute phase of TOS, with a possible activation of T-cells and release of cytokines, that could explain some of the clinical findings in this phase of the disease.