The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations ...with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.
Microparticles (MPs) which circulate within the plasma are elevated in patients with active pulmonary tuberculosis infection. Circulating MPs isolated from the plasma of patients with active ...pulmonary tuberculosis infection modulate the cytokine production of immune cells in vitro.
The rapid and persistent increase of drug-resistant
(
) infections poses increasing global problems in combatting tuberculosis (TB), prompting for the development of alternative strategies including ...host-directed therapy (HDT). Since
is an intracellular pathogen with a remarkable ability to manipulate host intracellular signaling pathways to escape from host defense, pharmacological reprogramming of the immune system represents a novel, potentially powerful therapeutic strategy that should be effective also against drug-resistant
. Here, we found that host-pathogen interactions in
-infected primary human macrophages affected host epigenetic features by modifying histone deacetylase (HDAC) transcriptomic levels. In addition, broad spectrum inhibition of HDACs enhanced the antimicrobial response of both pro-inflammatory macrophages (Mϕ1) and anti-inflammatory macrophages (Mϕ2), while selective inhibition of class IIa HDACs mainly decreased bacterial outgrowth in Mϕ2. Moreover, chemical inhibition of HDAC activity during differentiation polarized macrophages into a more bactericidal phenotype with a concomitant decrease in the secretion levels of inflammatory cytokines. Importantly,
chemical inhibition of HDAC activity in
-infected zebrafish embryos, a well-characterized animal model for tuberculosis, significantly reduced mycobacterial burden, validating our
findings in primary human macrophages. Collectively, these data identify HDACs as druggable host targets for HDT against intracellular
.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, usually chronic and has a progressive clinical course. Despite the availability of effective chemotherapy, TB is a ...leading killer of young adults worldwide and the global multi-drug resistant TB is reaching epidemic proportions. Interrupt transmission through early detection and treatment of the patients is a main element of the drug-resistant TB control strategy. However, many drugable targets in pathogens are already inhibited by current antibiotics and there is not a biomarker that indicate normal or pathogenic biological processes, or pharmacological responses to therapeutic intervention. Studies directed at evaluate key elements of host response to infection may identify biomarkers with measurable characteristics that indicate pathogenic biological processes. Cell-derived microparticles (MPs) are membrane-coated vesicles that represent subcellular elements and have been identified increasingly in a broad range of diseases and emerging as potential novel biomarker to pathological processes. In addition, MPs carry contents from their cells of origin as bioactive molecules as cytokines, enzymes, surface receptors, antigens and genetic information and may provide a means of communication between cells. Molecules-loaded MPs may interplay with the immune system and therefore can acts on inflammation, cell activation and migration. Therefore, MPs may be an important factor to immune process during Mtb infection, especially in pulmonary granulomas and influence the outcome of infection. Their characterization may facilitate an appropriate diagnosis, optimize pharmacological strategies and might be further explored as potential targets for future clinical interventions.
•Microparticles has a potential as biomarker for diagnosis and prognosis in patients with Tuberculosis.•Microparticles are a viable mechanism for the delivery of bioactive molecules involved in the immune response.•Microparticles can activate adaptive response without the necessity for direct antigen presenting cells and T cell contact.•Microparticles have the capacity of influence the outcome of Mycobacterium tuberculosis infection.
Systemic lupus erythematosus (SLE) is an autoimmune disease of the connective tissue with a large spectrum of clinical manifestations. Immune deregulation leads to autoantibody and immune complexes ...overproduction, complement activation, and persistent tissue inflammation. Considering that the current diagnosis depends on the interpretation of the complex criteria established by the American College of Rheumatology and that the disease course is characterized by unpredictable activations and remissions, each patient develops different manifestations, and therefore, the discovery of specific biomarkers is urgently required. Therefore, this study aimed to identify putative biomarkers for active and inactive SLE potentially capable in distinguishing laboratorial SLE from other autoimmune diseases. The 2D-DIGE proteomics technique was used to evaluate the differential abundance of proteins between patients with active SLE, inactive SLE, patients with other autoimmune disease, and healthy individuals. Six proteins showed increased abundance in active SLE (A) and inactive SLE (I) compared to the C and O groups, but not between groups A and I. There were two transthyretin (TTR) fragments or proteins with a structure similar to TTR (accession numbers: PDB: 1GKO_A and 2PAB_A), retinol-binding protein 4 (RBP4) isoform X1 (no information in databases such as UNIPROT), and antibody fragments. Two proteins, APO-AIV and SP-40,40, were upregulated in group A than in O and C and in group I versus C, but not in group I versus O. Therefore, we suggest these proteins to be considered as candidates for the diagnosis of SLE.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Pythium insidiosum immunomodulatory vaccine (PiV) has been tested in clinical and experimental pythiosis. Previous data showed that P. insidiosum immunogens have the ability to switch the Th2 immune ...response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c Leishmania infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential. Twenty-one days following challenge with L. major, large cutaneous granulomas developed in control mice, consistent with the expected Th2 response. In contrast, Leishmania-induced cutaneous lesions in PiV-immunized mice were minimal or absent. Flow cytometry analysis of spleen cells from mice immunized with PiV and subsequently challenged with L. major displayed more CD4+ and CD8+ cells than the control group. Moreover, spleen cells from mice that were immunized with PiV then challenged with L. major secreted high levels of IFN-γ, with a moderate IL-2, IL-4, and IL-10 mixed cytokine profile upon in vitro re-stimulation with PiV. Anti-P. insidiosum IgG1 in immunized animals was present at low titers suggesting a minor immunological role for this Ig isotype in this model. Our preliminary data showed that BALB/c mice challenged with L. major represent an attractive model in which to study PiV´s immunomodulatory properties.
Antigenic extracts from five Leishmania stocks were used to vaccinate C57BL/10 mice. The Leishvacin(R) and PH8 monovalent vaccine yielded the highest IFN-gamma levels in the supernatants of spleen ...cell culture from vaccinated animals. Each single strain immunized group showed evidence of protective immunity six months after the challenge with promastigotes of Leishmania (Leishmania) amazonensis. No differences were detected between the vaccinated groups. It can be concluded that vaccines composed of single Leishmania stocks can provide protection to C57BL/10 mice against L. (L.) amazonensis infection.
Tuberculosis (TB) is a lung disease caused by Mycobacterium tuberculosis. The interaction between the bacillus and the host may lead to a protective cellular immune response. In the present study, we ...propose the “in vitro” evaluation of this cellular immune response in patients with tuberculosis before and after chemotherapic treatment. Eleven patients with TB and 9 asymptomatic subjects with tuberculin skin test negative (TST–) (purified protein derivative (PPD) ≤10 mm) were evaluated. The peripheral lymphocytes of the subjects were analyzed utilizing the following surface markers: CD3+, CD4+, CD8+, CD19+, CD25+, CD56+, CD14+, CD16+ and HLA‐DR+. At the end of the treatment, symptomatic patients presented a significant predominance (P<0.05) of CD4+ lymphocytes, a significant decrease (P<0.05) in activated CD8+ T cells and a significant increase (P<0.05) in the marker CD19+. A predominance of mature NK cells and a significant decrease (P<0.05) in NKT cells were observed. Also observed was a trend toward decrease in immunoregulatory T cells and a predominance of pro‐inflammatory macrophages. TST– subjects presented a predominance of CD4+ over CD8+ and predominance of CD19+ and of mature NK cells in comparison to the group of patients, both before and after treatment. Thus, several cell types, such as CD4+ and CD8+ T cells, NK cells and their subpopulations, NKT cells and pro‐inflammatory macrophages could act in a synergic way to control the growth and multiplication of M. tuberculosis.
For decades thimerosal has been used as a preservative in the candidate
vaccine for cutaneous leishmaniasis, which was developed by Mayrink et
al. The use of thimerosal in humans has been banned due ...to its mercury
content. This study addresses the standardization of phenol as a new
candidate vaccine preservative. We have found that the proteolytic
activity was abolished when the test was conducted using the candidate
vaccine added to merthiolate (MtVac) as well as to phenol (PhVac). The
Montenegro's skin test conversion rates induced by MtVac and by
PhVac was 68.06% and 85.9%, respectively, and these values were
statistically significant (p < 0.05). The proliferative response of
peripheral mononuclear blood cells shows that the stimulation index of
mice immunized with both candidate vaccines was higher than the one in
control animals (p < 0.05). The ability of the candidate vaccines to
induce protection in C57BL/10 mice against a challenge with infective
Leishmania amazonensis promastigotes was tested and the mice immunized
with PhVac developed smaller lesions than the mice immunized with
MtVac. Electrophoresis of phenol-preserved antigen revealed a number of
proteins, which were better preserved in PhVac. These results do in
fact encourage the use of phenol for preserving the immunogenic and
biochemical properties of the candidate vaccine for cutaneous
leishmaniasis.
Prolonged storage of platelets could improve availability and logistical management and decrease wastage. Immunobiochemical methods can be used to guarantee the quality of platelets after prolonged ...storage.
The aim of this study was to compare storage-related changes in buffy coat-derived platelet concentrations versus platelet-rich plasmal.
Units of whole blood were drawn using a quadruple-bag blood container system. Platelet-rich plasma and buffy coat prepared from whole blood following standard methods were stored for 9 days. During this period test samples were aseptically collected for analysis on Days 1, 2, 3, 5, 7 and 9.
The highest CD42b expression was greater than 95%. The percentage of CD62p was significantly lower than the CD42b expression. The pH remained fairly stable during storage. Measurement of pO(2) and pCO(2) showed that oxygen levels were significantly higher than carbon dioxide levels. There were no significant differences in bicarbonate levels, glucose consumption and lactate production between the groups. The swirling effect with platelet-rich plasma samples decreased after 5 days of storage and after 7 days of storage for buffy coat samples. There was a significant twenty-fold increase in the mean IL-1β after 5 days of storage for both groups. Slight increases in IL-6 and IL-8 levels were seen at 5 days.
The quality of platelet concentrates remained acceptable during 7 days of storage in respect to the swirling effect, pH and platelet activation. There were no significant differences between buffy coat-derived platelets and platelet-rich plasma in this study.
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