Platelets immune response against Mycobacterium tuberculosis infection.

Tuberculosis (TB) is the first cause of death by a single infectious agent. Previous reports have highlighted the presence of platelets within Tb granulomas, albeit the immune-associated platelet response to Mycobacterium tuberculosis (Mtb) has not been deeply studied. Our results showed that platelets are recruited into the granuloma in the late stages of tuberculosis. Furthermore, electron-microscopy studies showed that platelets can internalize Mtb and produce host defense peptides (HDPs), such as RNase 7, HBD2 and hPF-4 that bind to the internalized Mtb. Mtb-infected platelets exhibited higher transcription and secretion of IL-1ß and TNF-α, whereas IL-10 and IL-6 protein levels decreased. These results suggest that platelets participate in the immune response against Mtb through HDPs and cytokines production.

[Células T reguladoras en lupus eritematoso generalizado].

El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune crónica caracterizada por la pérdida de la tolerancia a los antígenos propios y la síntesis de diferentes autoanticuerpos con la formación y depósito de complejos inmunes y el daño de múltiples órganos. Las células T reguladoras (Treg) desempeñan un papel esencial en el mantenimiento de la tolerancia periférica, controlan el estado de activación del sistema inmune y limitan las respuestas autoinmunes. El estudio del número y la función de las diferentes subpoblaciones de células Treg en LEG ha sido objeto de una intensa investigación. Dependiendo del fenotipo de las células Treg analizado se ha reportado que la frecuencia de estas células en pacientes con LEG se encuentra disminuida, aumentada o sin alteraciones. Además, diferentes grupos han descrito que la función supresora de las células Treg de los pacientes con LEG se encuentra reducida o no se ve afectada. En conjunto, lo datos reportados sugieren que las células Treg desempeñan un papel relevante en la patogénesis del LEG y que estos linfocitos pueden ser considerados blancos potenciales para el diseño de nuevas estrategias terapéuticas para esta enfermedad.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance to self-antigens and synthesis of different autoantibodies, with the formation and deposition of immune complexes and damage to multiple organs. T regulatory cells (Tregs) play a crucial role in maintaining peripheral tolerance, controlling the state of activation of the immune system and limiting autoimmune responses. The study of the number and function of the different Treg cell subpopulations in SLE has been the subject of intense research. Depending on the analyzed Treg cell phenotype, the frequency of these cells has been reported to be reduced, increased or unaltered in patients with SLE. In addition, different groups have described that Treg cells suppressive function is reduced or unaffected in patients with SLE. Taken together, the reported data suggest that Treg cells play a relevant role in the pathogenesis of SLE and that these lymphocytes can be considered potential targets for the design of new therapeutic strategies for this condition.

Patients with Systemic Lupus Erythematosus Show Increased Levels and Defective Function of CD69+ T Regulatory Cells.

T regulatory (Treg) cells have a key role in the pathogenesis of chronic inflammatory and autoimmune diseases. A CD4+CD69+ T cell subset has been described that behaves as Treg lymphocytes, exerting an important immune suppressive effect. In this study, we analyzed the levels and function of CD4+CD69+ Treg cells in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels of CD4+CD69+ Treg cells were analyzed by multiparametric flow cytometry, and their function was measured by an assay of suppression of lymphocyte activation and through the inhibition of cytokine synthesis. We found an increased percent of CD4+CD25varCD69+TGF-ß+IL-10+Foxp3- lymphocytes in patients with SLE compared to controls. In addition, a significant diminution in the suppressive effect of these cells on the activation of autologous T lymphocytes was observed in most patients with SLE. Accordingly, CD69+ Treg cells from SLE patients showed a defective capability to inhibit the release of IL-2, IL-6, IL-10, and IL-17A by autologous lymphocytes. Our findings suggest that while CD4+CD69+ Treg lymphocyte levels are increased in SLE patients, these cells are apparently unable to contribute to the downmodulation of the autoimmune response and the tissue damage seen in this condition.

Innate pro-B-cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells.

Diverse hematopoietic progenitors, including myeloid populations arising in inflammatory and tumoral conditions and multipotent cells, mobilized by hematopoietic growth factors or emerging during parasitic infections, display tolerogenic properties. Innate immune stimuli confer regulatory functions to various mature B-cell subsets but immature B-cell progenitors endowed with suppressive properties per se or after differentiating into more mature regulatory B cells remain to be characterized. Herein we provide evidence for innate pro-B cells (CpG-proBs) that emerged within the bone marrow both in vitro and in vivo upon Toll-like receptor-9 activation and whose adoptive transfer protected nonobese diabetic mice against type 1 diabetes (T1D). These cells responded to IFN-γ released by activated effector T cells (Teffs), by up-regulating their Fas ligand (FasL) expression, which enabled them to kill Teffs through apoptosis. In turn, IFN-γ derived from CpG-proBs enhanced IFN-γ while dramatically reducing IL-21 production by Teffs. In keeping with the crucial pathogenic role played by IL-21 in T1D, adoptively transferred IFN-γ-deficient CpG-proBs did not prevent T1D development. Additionally, CpG-proBs matured in vivo into diverse pancreatic and splenic suppressive FasL(high) B-cell subsets. CpG-proBs may become instrumental in cell therapy of autoimmune diseases either on their own or as graft complement in autologous stem cell transplantation.

CCL22-producing CD8α- myeloid dendritic cells mediate regulatory T cell recruitment in response to G-CSF treatment.

G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local recruitment of T regulatory cells (Tregs). This is an indirect effect because adoptive transfer of G-CSF-induced tolerogenic dendritic cells (DCs) promotes Treg accumulation. However, the identity of the particular DC subset and the molecule(s) mediating this effect remain unknown. We demonstrate in this study that the adoptive transfer of CD11c(high)CD8α(-) DCs isolated from pegylated G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the pancreatic recruitment of CD4(+)CD25(+)Foxp3(+) Tregs, which generated increased amounts of TGF-ß. Likewise, only CD11c(high)CD8α(-) DCs from pegG-CSF recipients secreted the chemokine CCL22 at levels that effectively attracted Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes compared with those from the spleen. Accordingly, CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes of pegG-CSF recipients were more efficient than their splenic counterparts in the recruitment of Tregs upon adoptive transfer. Predictably, CD11c(high)CD8α(-) DCs failed to recruit these Tregs both in vivo and in vitro following intracellular neutralization of CCL22. These data assign a key role to CD8α(-) DCs and CCL22 in Treg recruitment in the protection of NOD mice against type 1 diabetes following the treatment with G-CSF.

Expression and function of dectin-1 is defective in monocytes from patients with systemic lupus erythematosus and rheumatoid arthritis.

The aim of this work was to study the expression and function of the innate immune receptor dectin-1 in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We studied twenty-six patients with SLE not receiving immunosuppressive therapy, twenty-six patients with RA, and fifteen controls. We found that monocytes from SLE patients showed a diminished expression of dectin-1 compared to healthy controls, and an inverse correlation between percent of dectin-1(+) cells and the disease activity score was detected. In addition, cells from SLE patients showed an abnormal calcium flux response induced by dectin-1 ligands as well as an enhanced release of IL-1ß, IL-6 and TNF-α, but not IL-23, upon dectin-1 engagement. Monocytes from patients with RA also showed a diminished expression, and a defective function of dectin-1. Our data suggest that dectin-1 receptor defects could contribute to the pathogenesis of autoimmune inflammatory conditions.

Induction of Th17 lymphocytes and Treg cells by monocyte-derived dendritic cells in patients with rheumatoid arthritis and systemic lupus erythematosus.

Dendritic cells (DCs) have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg) lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10) conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions.

Relationship of Serum Zinc Levels with Cardiometabolic Traits in Overweight and Obese Schoolchildren from Mexico City.

Zinc (Zn) participates as a cofactor for many enzymes in the cellular metabolism, and its serum levels have been associated with different metabolic diseases, especially obesity (OB). Nevertheless, its associations are not clear in the children population. The objective of this study is to evaluate the association between serum Zn levels (SZn) with overweight/obesity status (OW/OB), as well as its cardiometabolic traits in a population of children in Mexico City. Anthropometrical data (body mass index z score (BMIz)), demographic variables (age and sex), and cardiometabolic traits (total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), fasting plasma glucose (FPG), and insulin) were analyzed in this cross-sectional study. SZn were measured by inductively coupled plasma mass spectrometry (ICP-MS). The population included 210 children from Mexico City (girls (n = 105) and boys (n = 105)) between ages 6 and 10 years. Normal-weight (NW) schoolchildren had higher SZn concentrations (66 µg/dL; IQR: 48 to 91) compared to OW or OB schoolchildren (61 µg/dL; IQR: 45 to 76). The data showed a significant negative association between SZn and BMIz without sex exclusion (r = - 0.181 and p = 0.009). The boy's population did not show an association between the SZn and BMIz compared to the girl's population which showed a significant negative association (r = - 0.277 and p = 0.004). In addition, other associations were found between SZn and TC (boys (r = 0.214 and p = 0.025), LDLc (boys (r = 0.213 and p = 0.029), and TG (girls (r = - 0.260 and p = 0.007)). Moreover, 38.6% of the total children in our population study had Zn deficiency (ZnD). NW schoolchildren had higher SZn concentrations compared to OW or OB schoolchildren. A diet low in Zn can be a factor to evaluate in the development of childhood OB in Mexico. However, further studies need to be performed on the children Mexican population to replicate and confirm our findings.

Altered Phenotype of Circulating Dendritic Cells and Regulatory T Cells from Patients with Acute Myocarditis.

Dendritic cells (DCs) and regulatory T cells (Tregs) play an essential role in myocarditis. However, a particular DC phenotype in this disease has not been assessed. Herein, we aim to evaluate myeloid (mDCs) and plasmacytoid DC (pDC) phenotype, as well as Treg levels from myocarditis patients and healthy controls. Using multiparametric flow cytometry, we evaluated the levels of myeloid DCs (mDCs), plasmacytoid DCs (pDCs), and Tregs in peripheral blood from myocarditis patients (n = 16) and healthy volunteers (n = 16) and performed correlation analysis with clinical parameters through Sperman test. DCs from myocarditis patients showed a higher expression of costimulatory molecules while a diminished expression of the inhibitory receptors, ILT2 and ILT4. Even more, Treg cells from myocarditis patients displayed higher levels of FOXP3 compared to controls. Clinically, the increased levels of mDCs and their higher expression of costimulatory molecules correlate with a worse myocardial function, higher levels of acute phase reactants, and higher cardiac enzymes. This study shows an activating phenotype of circulating DCs from myocarditis patients. This proinflammatory status may contribute to the pathogenesis and immune deregulation in acute myocarditis.

GPR15 expressed in T lymphocytes from RA patients is involved in leukocyte chemotaxis to the synovium.

The rheumatoid arthritis (RA) inflammatory process occurs in the joints where immune cells are attracted into the synovium to promote remodeling and tissue damage. GPR15 is a G protein-coupled receptor (GPCR) located on chromosome 3 and has similarity in its sequence with chemokine receptors. Recent evidence indicates that GPR15 may be associated with modulation of the chronic inflammatory response. We evaluated the expression of GPR15 and GPR15L in blood and synovial tissue samples from RA patients, as well as to perform a functional migration assay in response to GPR15L. The expression of GPR15 and c10orf99/gpr15l mRNA was analyzed by RT-qPCR. Samples of synovial fluid and peripheral blood were analyzed for CD45+CD3+CD4+GPR15+ and CD45+CD3+CD8+GPR15+ T cell frequency comparing RA patients versus control subjects by flow cytometry. Migration assays were performed using PBMCs isolated from these individuals in response to the synthetic GPR15 ligand. Statistical analysis included Kruskal-Wallis test, T-test, or Mann-Whitney U test, according to data distribution. A higher expression in the mRNA for GPR15 was identified in early RA subjects. The frequencies of CD4+/CD8+ GPR15+ T lymphocytes are higher in RA patients comparing with healthy subjects. Also, the frequency CD4+/CD8+ GPR15+ T lymphocytes are higher in synovial fluid of established RA patients comparing with OA patients. GPR15 and GPR15L are present in the synovial tissue of RA patients and GPR15L promotes migration of PBMCs from RA patients and healthy subjects. Our results suggest that GPR15/GPR15L have a pathogenic role in RA and their antagonizing could be a therapeutic approach in RA.

Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors.

Mechanisms of protection against autoimmune diseases by transplantation of autologous hematopoietic progenitors remain poorly defined. We recently demonstrated that, unlike medullary hematopoietic stem cells (HSCs), mobilized hematopoietic progenitors (HPCs) stimulate peripheral Foxp3(+) regulatory T cell (Treg)-expansion through cell-contact activation of Notch signaling and through as yet undetermined soluble factor(s), distinct from TGF-beta1. Herein we identified one such soluble factor as granulocyte macrophage-colony stimulating factor (GM-CSF), which is produced at higher levels by HPCs than HSCs and whose neutralization significantly reduces the growth-promoting effect of HPCs on Treg. Treg express a functional GM-CSF receptor alpha-chain CD116 and proliferate in response to this cytokine independently from IL2. GM-CSF-expanded Treg-like HPC-expanded Treg-display enhanced suppressive capacity relative to control Treg. Hence, mobilized progenitors stimulate Treg expansion both by cell-contact dependent mechanisms and by their production of GM-CSF.

Chemoresistance in Breast Cancer Patients Associated With Changes in P2X7 and A2A Purinergic Receptors in CD8+ T Lymphocytes.

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival. Although emerging evidence indicates a key role of the purinergic receptors P2X7 and A2A in cancer, less is known about their involvement in BRCA chemoresistance. In this sense, as the chemotherapeutic treatment stimulates immune system response, we evaluated the expression and function of P2X7 and A2A receptors in CD8+ T cells before and four months after BRCA patients received neoadjuvant chemotherapy. The results showed an increase in the levels of expression of P2X7 and a decrease in the expression of A2A in CD8+ T cells in non-chemoresistant (N-CHR) patients, compared to chemoresistant (CHR) patients. Interestingly, in CHR patients, reduced expression of P2X7 occurs along with a decrease in the CD62L shedding and the production of IFN-γ. In the case of the A2A function, the inhibition of IFN-γ production was not observed after chemotherapy in CHR patients. A possible relationship between the modulation of the expression and function of the P2X7 and A2A receptors was found, according to the molecular subtypes, where the patients that were triple-negative and human epidermal growth factor receptor 2 (HER2)-enriched presented more alterations. Comorbidities such as overweight/obesity and type 2 diabetes mellitus (T2DM) participate in the abnormalities detected. Our results demonstrate the importance of purinergic signaling in CD8+ T cells during chemoresistance, and it could be considered to implement personalized therapeutic strategies.

Analysis of Sodium Chloride Intake and Treg/Th17 Lymphocytes in Healthy Individuals and Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus.

We assessed different immune parameters in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with low (LSI) and high (HSI) sodium intake. Thirty-eight patients with RA, thirty-seven with SLE, and twenty-eight healthy subjects were studied and classified as LSI or HSI. Levels and suppressive function of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were determined by flow cytometry in blood samples. Levels and in vitro differentiation of Th17 cells were also assessed. Similar levels of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were observed in LSI and HSI patients or controls. However, a positive correlation was detected between sodium intake and levels of CD4+CD25+Foxp3+ Treg cells in SLE and a negative association between CD4+CD69+Foxp3- Treg cells and sodium intake in RA. No other significant associations were detected, including disease activity and sodium intake. Moreover, the suppressor activity of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells was similar in LSI and HSI patients or controls. The levels and in vitro differentiation of Th17 cells were also similar in LSI and HSI individuals. Our results suggest that, in the population studied (Mexican mestizo), the level of sodium intake is not apparently associated with different relevant immune parameters in healthy subjects or patients with SLE or RA.

FICZ generates human tDCs that induce CD4+ CD25high Foxp3+ Treg-like cell differentiation.

Dendritic cells (DCs) play a central role in the maintenance of immune homeostasis, their participation as professional antigen presenting cells is essential to the initiation of the adaptive immune response as well as to the induction of tolerance. The recently described role of the aryl hydrocarbon receptor (AhR) in the immune system, particularly in the modulation of the adaptive immune response has attracted the attention as a potential player in the induction of immune tolerance. However, the effects of AhR activation through endogenous ligands on human DCs have been poorly evaluated. In this study, we investigated the effect of FICZ, a natural AhR ligand, on monocyte-derived dendritic cells (Mo-DCs) from healthy subjects. We found that the activation of AhR through FICZ during DCs differentiation and maturation processes resulted in a decreased expression of CD83, an increased expression of the enzyme IDO and a reduced production of the pro-inflammatory cytokines IL-6 and TNF-α. More importantly, FICZ-treated DCs were able to induce the differentiation of naive T lymphocytes into CD4+ CD25high Foxp3+ T reg-like cells. Our results show that the activation of the AhR on human DCs induces a tolerogenic phenotype with potential implications in immunotherapy.

Calcitriol promotes proangiogenic molecules in keratinocytes in a diabetic foot ulcer model.

Foot ulceration is one of the most common and complex sequelae of diabetes mellitus, generally posing a therapeutic challenge due to poor healing responses and high rates of complications, including peripheral vascular disease, ischemia and infections. Calcitriol, the most active vitamin D metabolite, induces antimicrobial peptides production in keratinocytes from diabetic foot ulcers (DFU); however, little is known about its effects on angiogenic factors in this pathology. Herein we aimed at studying whether calcitriol induces angiogenic molecules in keratinocytes under normoxic and hypoxic conditions, and if these molecules are able to improve cell migration in vitro. Evaluation of DFU samples by immunohistochemistry showed increased VEGF and decreased angiogenin and HIF-1α expression compared to controls, suggesting an altered pattern of angiogenic factors in DFU. Interestingly, incubation of keratinocytes with calcitriol significantly upregulated VEGFA, HIF-1α and angiogenin gene expression, while the resulting cell culture media stimulated both endothelial cells and keratinocytes migration in an in vitro wound closure assay under a normoxic environment (p<0.05). Moreover, the culture media of calcitriol-treated keratinocytes stimulated cell migration in a similar extent as exogenous VEGF or EGF in endothelial and keratinocytes cells. These results suggest that the altered profile of angiogenic molecules in DFU might be improved by local or systemic treatment with calcitriol under normoxic conditions, which could probably be achieved with hyperbaric oxygen therapy. Given that calcitriol not only augments proangiogenic factors but also induces antimicrobial peptides expression, this hormone should be further investigated in clinical trials of DFU.

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets.

Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60µM NAD. In contrast, P2Xs receptor-dependent proliferation with 300µM ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD.

T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide.

The CD43 coreceptor molecule has been shown to participate in lymphocyte adhesion and activation. Leukocyte homotypic aggregation results from a cascade of intracellular signals delivered to the cells upon engagement of different cell-surface molecules with their natural ligands. This phenomenon requires an active metabolism, reorganization of the cytoskeleton, and relocalization of cell-surface molecules. The aim of this study was to identify some of the key members of the signaling cascade leading to T lymphocyte homotypic aggregation following CD43 engagement. CD43-mediated homotypic aggregation of T lymphocytes required the participation of Src kinases, phospholipase C-gamma2, protein kinase C, phosphatidylinositol-3 kinase, as well as extracellular-regulated kinase 1/2 and p38. Data shown here suggest that these signaling molecules play a central role in regulating actin cytoskeleton remodeling after CD43 ligation. We also evaluated the ability of immunomodulatory drugs such as leflunomide to block the CD43-mediated homotypic aggregation. Leflunomide blocked the recruitment of targets of the Src family kinases as well as actin polymerization, diminishing the ability of T lymphocytes to aggregate in response to CD43-specific signals, suggesting that this drug might control the migration and recruitment of lymphoid cells to inflamed tissues.

Analysis of bacterial communities of infected primary teeth in a Mexican population

BACKGROUND: The objective of this study was to describe the bacterial communities associated with pediatric patients with endodontic infections of temporal teeth by targeting the 16S rRNA gene using pyrosequencing. MATERIAL AND METHODS: Microbiological samples were obtained from the lower primary molars of thirteen 13 pediatric patients with dental infections. An aspiration method for microbiological sampling was used. The identification of microbiota employing the pyrosequencing method by targeting the 16S gene was performed. RESULTS: Ribosomal 16S RNA gene sequences were amplified, obtaining a total of 16,182 sequences from 13 primary infected molars (13 different individuals) by pyrosequencing. Bacteroidetes phyla (35.15%) were the most abundant followed by Firmicutes (33.3%) and Fusobacteria (10.05%); the presence of specific pathogenic bacteria was determined as well. CONCLUSIONS: The infected root canal of primary teeth contains a high diversity of anaerobic bacteria, and Bacteroidetes, Firmicutes, and Fusobacteria phyla were the most abundant; Prevotella and Streptococcus genera were the most prevalent

No disponible

Rolipram inhibits polarization and migration of human T lymphocytes.

Phosphodiesterase inhibitors possess anti-inflammatory and immunomodulatory properties and seem to have a great potential in the treatment of inflammatory skin diseases; however, an overall study on the effects of specific phosphodiesterase inhibitors, such as rolipram on the processes involved in the extravasation of lymphoid cells has not been performed. In this work we have assessed the effect of rolipram on the adhesion, polarization, and migration of normal human T lymphocytes. We found that low concentrations of rolipram were able to inhibit significantly the adhesion of T cells to the beta1 and beta2 integrin ligands vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. Rolipram also interfered with the activation of integrins, and significantly inhibited the homotypic aggregation of T lymphocytes induced by anti-beta1 and anti-alpha4 integrin chain monoclonal antibodies. In addition, rolipram had a downregulatory effect on the activation of T cells, and significantly diminished the expression of the activation antigens CD69, CD25, and CD98 induced by phytohemagglutinin. Finally, this drug inhibited the polarization and transendothelial migration of T lymphocytes induced by the chemokine CXCL12 (SDF-1) and the chemotactic cytokine interleukin-15. The results indicate that rolipram, at low concentrations, exerts an important anti-inflammatory and immunomodulatory effect, and suggest that this selective phosphodiesterase inhibitor may be an effective tool for the therapy of immune-mediated diseases.

Células T reguladoras en lupus eritematoso generalizado / Regulatory T cells in systemic lupus erythematosus

Resumen El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune crónica caracterizada por la pérdida de la tolerancia a los antígenos propios y la síntesis de diferentes autoanticuerpos con la formación y depósito de complejos inmunes y el daño de múltiples órganos. Las células T reguladoras (Treg) desempeñan un papel esencial en el mantenimiento de la tolerancia periférica, controlan el estado de activación del sistema inmune y limitan las respuestas autoinmunes. El estudio del número y la función de las diferentes subpoblaciones de células Treg en LEG ha sido objeto de una intensa investigación. Dependiendo del fenotipo de las células Treg analizado se ha reportado que la frecuencia de estas células en pacientes con LEG se encuentra disminuida, aumentada o sin alteraciones. Además, diferentes grupos han descrito que la función supresora de las células Treg de los pacientes con LEG se encuentra reducida o no se ve afectada. En conjunto, lo datos reportados sugieren que las células Treg desempeñan un papel relevante en la patogénesis del LEG y que estos linfocitos pueden ser considerados blancos potenciales para el diseño de nuevas estrategias terapéuticas para esta enfermedad.

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance to self-antigens and synthesis of different autoantibodies, with the formation and deposition of immune complexes and damage to multiple organs. T regulatory cells (Tregs) play a crucial role in maintaining peripheral tolerance, controlling the state of activation of the immune system and limiting autoimmune responses. The study of the number and function of the different Treg cell subpopulations in SLE has been the subject of intense research. Depending on the analyzed Treg cell phenotype, the frequency of these cells has been reported to be reduced, increased or unaltered in patients with SLE. In addition, different groups have described that Treg cells suppressive function is reduced or unaffected in patients with SLE. Taken together, the reported data suggest that Treg cells play a relevant role in the pathogenesis of SLE and that these lymphocytes can be considered potential targets for the design of new therapeutic strategies for this condition.