Publications by authors named "Cristiane Bani Correa"

16 Publications

  • Page 1 of 1

Functional and concurrent training do not impair immune function and improve functional fitness in postmenopausal women: A randomized controlled trial.

Exp Gerontol 2021 10 31;153:111504. Epub 2021 Jul 31.

Department of Physical Education, Post Graduate Program in Physical Education and Post Graduate Program in Physiology Sciences, Center of Biological and Health Sciences, Federal University of Sergipe, São Cristóvão, Brazil.

Purpose: To evaluate the effects of functional and concurrent training on immune function and functional fitness in postmenopausal women.

Materials And Methods: A randomized controlled trial was performed on 108 women aged 60 or older who were randomly assigned among the groups: control group (CG: n = 40; 63.88 ± 3.64 years); functional training (FT: n = 32; 63.88 ± 3.79 years); and concurrent training (CT: n = 36; 64.83 ± 4.00 years). Immune function was measured by the expression of the T-lymphocyte function-related surface markers (CD28 and CD57). Functional fitness was assessed using physical tests similar to daily activities, i.e., five times sit to stand, timed up and go, and gallon-jug shelf-transfer.

Results: Regarding immune function, there was only a time effect, without between-group differences. Specifically, FT and CT show a reduction and increase in CD4 and CD8 T cells, respectively, without impairment in the subpopulations analyzed, while CG showed a reduction in naive T cells (CD8CD28). For functional fitness tests, there was a time × group interaction effect for all tests, the FT and CT were superior to the CG, with FT showing differences after the fourth week, while the CT showed this effect after the eighth week of intervention.

Conclusion: FT and CT do not impair immune function and similarly improve functional fitness in postmenopausal women.

Clinical Trials Registry: RBR-2d56bt.
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http://dx.doi.org/10.1016/j.exger.2021.111504DOI Listing
October 2021

Nisin Induces Cell-Cycle Arrest in Free-Living Amoebae Acanthamoeba castellanii.

Acta Parasitol 2021 Jun 22. Epub 2021 Jun 22.

Laboratório de Entomologia e Parasitologia Tropical, Departamento de Morfologia, Universidade Federal de Sergipe, São Cristóvão, Sergipe, 49100-000, Brazil.

Purpose: Acanthamoeba spp. are free-living amoebas with worldwide distribution and play an important role as disease-causing agents in humans. Drug inability to completely eradicate these parasites along with their toxic effects suggest urgent need for new antimicrobials. Nisin is a natural antimicrobial peptide produced by Lactococcus lactis. Nisin is also the only bacteriocin approved for use in food preservation. In this work, we analyzed the effect of nisin on the growth of Acanthamoeba castellanii trophozoites.

Methods: A total of 8 × 10 trophozoites were exposed to increasing concentrations of nisin to determine its activity. Changes in cell membrane and cellular cycle of trophozoites were investigated by flow cytometry, and nisin cytotoxicity in mammalian cells was evaluated in L929 cells by MTT method.

Results: After 24 h exposure to increasing nisin concentrations, an IC of 4493.2 IU mL was obtained for A. castellanii trophozoites. However, after 72 h a recovery in amoebic growth was observed, and it was no longer possible to determine IC. Flow cytometry analysis showed that nisin has no effect on the membrane integrity. Treatment with nisin induced cell-cycle arrest during G1 and S phases in A. castellanii trophozoites, which recovered their growth after 72 h.

Conclusion: This is one of the first studies showing the effect of internationally approved nisin against A. castellanii trophozoites. Nisin caused cell-cycle arrest in trophozoites, momentarily interfering with the DNA replication process. The data highlight the amoebostatic activity of nisin, and suggest its use as an adjuvant for the treatment of infections caused by Acanthamoeba spp.
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http://dx.doi.org/10.1007/s11686-021-00436-xDOI Listing
June 2021

Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell.

BMC Cancer 2021 Jun 2;21(1):662. Epub 2021 Jun 2.

Laboratory of Biology and Immunology of Cancer and Leishmania, Department of Morphology, Federal University of Sergipe, São Cristóvão, Sergipe, Brasil.

Background: Melanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells.

Methods: The Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability.

Results: In pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC), and the compound 9, that has IC 5.3 μM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 μM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells.

Conclusions: The results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).
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http://dx.doi.org/10.1186/s12885-021-08404-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173884PMC
June 2021

Seroprevalence of SARS-CoV-2 antibodies in the poorest region of Brazil: results from a population-based study.

Epidemiol Infect 2021 05 18;149:e130. Epub 2021 May 18.

Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil.

Population-based seroprevalence studies on coronavirus disease 2019 (COVID-19) in low- and middle-income countries are lacking. We investigated the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies in Sergipe state, Northeast Brazil, using rapid IgM-IgG antibody test and fluorescence immunoassay. The seroprevalence was 9.3% (95% CI 8.5-10.1), 10.2% (95% CI 9.2-11.3) for women and 7.9% (IC 95% 6.8-9.1) for men (P = 0.004). We found a decline in the prevalence of SARS-CoV-2 antibodies according to age, but the differences were not statistically significant: 0-19 years (9.9%; 95% CI 7.8-12.5), 20-59 years (9.3%; 95% CI 8.4-10.3) and ≥60 years (9.0%; 95% CI 7.5-10.8) (P = 0.517). The metropolitan area had a higher seroprevalence (11.7%, 95% CI 10.3-13.2) than outside municipalities (8.0%, 95% CI 7.2-8.9) (P < 0.001). These findings highlight the importance of serosurveillance to estimate the real impact of the COVID-19 outbreak and thereby provide data to better understand the spread of the virus, as well as providing information to guide stay-at-home measures and other policies. In addition, these results may be useful as basic data to follow the progress of COVID-19 outbreak as social restriction initiatives start to be relaxed in Brazil.
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http://dx.doi.org/10.1017/S0950268821001163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160491PMC
May 2021

Aberrant Phenotypes in Acute Myeloid Leukemia and Its Relationship with Prognosis and Survival: A Systematic Review and Meta-Analysis.

Int J Hematol Oncol Stem Cell Res 2020 Oct;14(4):274-288

Department of Pharmacy, Laboratory of Hematology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.

: The aim of this review was to evaluate the influence of aberrant phenotypes in prognosis and survival in acute myeloid leukemia (AML) patients by multiparametric flow cytometry. : Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a review of PubMed, Scopus, Science Direct and Web of Science was carried out through 1998 to 2016, conducted by two reviewers independently, evaluating titles, abstracts and full-texts of the selected studies. : Ten studies were included on this review, in which the aberrant phenotype expression of 17 markers were detected in AML patients. From these, 11 aberrant phenotypes were associated with prognosis, which eight had shown negative impact on prognosis: CD7, CD56, CD15, CD2, CD3, CD90, CD123, CD117, and three others were associated with good prognosis: CD19, CD98 and CD117/CD15. Meta-analysis showed that aberrant expression of CD56 as a poor prognostic marker with unfavorable outcomes is implicated in decreased overall survival in AML patients in 28 months (95% CI: 0.62 to 0.92). This was observed when there was association between CD56 expression and other prognostic factors, influencing on patients' management care and treatment.
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http://dx.doi.org/10.18502/ijhoscr.v14i4.4484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876425PMC
October 2020

Biochanin A attenuates zymosan-induced arthritis in mice similarly to 17-β estradiol: an alternative to hormone replacement therapy?

Inflamm Res 2020 Dec 25;69(12):1245-1256. Epub 2020 Sep 25.

Postgraduate Program in Physiological Sciences, Cellular Migration Laboratory, Federal University of Sergipe, São Cristovão, Brazil.

Objective And Design: Biochanin A (BCA), a phytoestrogen, has various pharmacological properties. This study was conducted to compare BCA's therapeutic property against 17-β estradiol replacement therapy in zymosan-induced arthritis (ZIA) in mice. Additionally, we further investigated in vitro the anti-inflammatory action on neutrophils.

Treatment: Ovariectomized (OVX) and non-OVX mice were pretreated with BCA (1, 3 and 9 mg/kg) or estrogen (50 µg/kg) for 14 days prior to ZIA. Neutrophils were pretreated with BCA (1, 10 and 100 μM) for 1 h prior to phorbol 12-myristate 13-acetate.

Methods: Anti-inflammatory effects of BCA were evaluated by cellular infiltrate, paw edema and cytokine measurement. In vitro, apoptosis was assessed by morphology and flow cytometry. Neutrophil extracellular traps (NET) were determined by fluorescent microscopy and DNA release. Statistical differences were determined by one- or two-way ANOVA.

Results: BCA inhibited neutrophil accumulation, paw edema and proinflammatory cytokine (TNF-α and IFN-γ) and increased anti-inflammatory cytokines (IL-4 and IL-10) in OVX and non-OVX mice, similar to 17-β estradiol replacement therapy. In vitro, BCA increased apoptosis and consequently reduced NETs.

Conclusion: BCA has a notable anti-inflammatory effect, similar to 17-β estradiol, and is especially effective for treatment of ZIA. These results suggest that BCA may be promising for the treatment of postmenopausal arthritis.
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http://dx.doi.org/10.1007/s00011-020-01403-4DOI Listing
December 2020

Mass spectrometry characterization, antioxidant activity, and cytotoxicity of the peel and pulp extracts of Pitomba.

Food Chem 2021 Mar 31;340:127929. Epub 2020 Aug 31.

Post-Graduate Program in in Nutrition Science, Federal University of Sergipe (UFS), Av. Marechal Rondon, S / n - Jardim Rosa Elze, São Cristóvão, SE 49100-000, Brazil.

The fruit of the Talisia esculenta tree, is largely consumed and appreciated for its bittersweet taste; however, detailed information on its constituent bioactive compounds is still scarce. Therefore, this study aims to screen the antioxidant activity by six methods and determine the chemical profile of the pitomba fruit peel and pulp by electrospray ionization-Fourier transform-mass spectrometry. This is the first study attempting to identify the bioactive compounds in the pitomba fruit peel. Consequently, 19 and 14 compounds were identified in the ethanolic and hexanic peel extracts, while 7 and 10 compounds were detected in the ethanolic and hexanic pulp extracts, respectively. The common compounds across the board were citric acid, ascorbic acid, and shikimic acid. In addition, the ethanolic peel extract exhibited a high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (54.21-81.41%). The obtained results highlight the importance the pitomba fruit as a promising source of natural compounds with high antioxidant activities.
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http://dx.doi.org/10.1016/j.foodchem.2020.127929DOI Listing
March 2021

In situ photocrosslinkable formulation of nanocomposites based on multi-walled carbon nanotubes and formononetin for potential application in spinal cord injury treatment.

Nanomedicine 2020 10 27;29:102272. Epub 2020 Jul 27.

Tiradentes University (UNIT), Aracaju/SE, Brazil; Technology and Research Institute (ITP), Aracaju/SE, Brazil. Electronic address:

Carbon nanotubes (CN) have been studied to treat spinal cord injuries because of its electrical properties and nanometric dimensions. This work aims to develop a photopolymerizable hydrogel containing CN functionalized with an anti-inflammatory molecule to be used in situ on spinal cord injuries. The CN functionalization step was done using the drug (formononetin). The nanocomposites were characterized by morphological analysis, FTIR, Raman Spectroscopy, thermal analysis and cytotoxicity assays (MTT and HET-CAM). The nanocomposites were incorporated into gelatin methacryloyl hydrogel and exposed to UV light for photopolymerization. The volume of the formulation and the UV exposition time were also analyzed. The CN characterization showed that formononetin acted as a functionalization agent. The functionalized CN showed safe characteristics and can be incorporated in photocrosslinkable formulation. The UV exposition time for the formulation photopolymerization was compatible with the cell viability and also occurred in the injury site.
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http://dx.doi.org/10.1016/j.nano.2020.102272DOI Listing
October 2020

Antimicrobial activity of Lippia gracilis essential oils on the plant pathogen Xanthomonas campestris pv. campestris and their effect on membrane integrity.

Pestic Biochem Physiol 2019 Oct 26;160:40-48. Epub 2019 Jun 26.

Departamento de Fisiologia, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil. Electronic address:

Xanthomonas campestris pv.campestris (Xcc) is the causative agent of black rot, a disease that causes serious damage to plants from Brassicaceae family. However, there are no chemicals or biological agent commercially registered for the control of this disease. Thus, this study aimed to evaluate the antimicrobial activity and chemical composition of Lippia gracilis essential oils (EOs) on Xcc aiming its use as effective biological control. We also investigated the effect of EOs on the integrity of the bacterial cytoplasmic membrane. Chemical analysis by GC/MS showed that the major compounds of the seven EOs of L. gracilis are thymol or carvacrol. The seven genotypes showed inhibition of bacterial growth with MIC from 700 μg.ml to 1000 μg.ml, with the genotype LGRA-106 (rich in Thymol) with higher antimicrobial activity. The MIC for thymol and carvacrol were 250 μg.ml. After exposure to LGRA-106 EO (2×, 1×, 1/2×, 1/4×, and 1/8 x MIC for 5 min, it was observed a decreased cell viability and increased pI fluorescence, which indicates damage to the cytoplasmic cell membrane. This study demonstrates that L. gracilis EOs have antimicrobial activity and have a potential to be used in the control of black rot. Furthermore this antimicrobial activity is due, at least in part, to bacterial cytoplasmic membrane damage.
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http://dx.doi.org/10.1016/j.pestbp.2019.06.014DOI Listing
October 2019

Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy.

Front Immunol 2018 12;9:2920. Epub 2018 Dec 12.

Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil.

Leprosy is a chronic disease caused by infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts ( cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against infection that prevents the development of leprosy. These data further our understanding of infection/leprosy and are instructive for vaccine development.
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http://dx.doi.org/10.3389/fimmu.2018.02920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315144PMC
October 2019

Protective effect of carvacrol on acetic acid-induced colitis.

Biomed Pharmacother 2017 Dec 7;96:313-319. Epub 2017 Oct 7.

Department of Physiology, Federal University of Sergipe (UFS), São Cristóvão, SE, Brazil. Electronic address:

The pharmacological therapy for inflammatory bowel diseases continues to be problematic, and requires new alternative options. In this study, we tested the hypothesis that carvacrol (CAR), a phenolic monoterpene with anti-inflammatory and antioxidant activities, can treat experimental colitis in mice. C57BL/6 mice (n=8/group) were subjected to intrarectal administration of acetic acid (5%) to induce colitis. Mice were pretreated with CAR (25, 50 or 100mg/kg, p.o.) every 12h for three days prior to the induction. Abdominal hyperalgesia, macroscopic and microscopic colon damage, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, oxidative stress markers, and antioxidant enzyme activities were evaluated. Pretreatment with all doses of CAR significantly decreased abdominal hyperalgesia and colon MPO activity and TNF-α and IL-1β levels. A reduction in macroscopic and microscopic damage (p<0.05) was observed at doses of 50 and 100mg/kg CAR. Pretreatment with CAR significantly reduced lipid peroxidation (for all doses) and increased sulfhydryl groups (at 100mg/kg). This effect was accompanied by a significant increase in catalase, superoxide dismutase, and glutathione peroxidase activities. These findings indicate that CAR protected mice from acetic acid-induced colitis by reducing inflammatory, nociceptive, and oxidative damages.
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http://dx.doi.org/10.1016/j.biopha.2017.10.017DOI Listing
December 2017

F1 Domain of the Nucleoside Hydrolase Promotes a Th1 Response in Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis.

Front Immunol 2017 12;8:750. Epub 2017 Jul 12.

Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

The nucleoside hydrolase NH36 is the main antigen of the Leishmune vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with from an endemic area of visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42-43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion was determined by F1, a granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the infection by . In addition, F1 and NH36 discriminated the IgG3 humoral response in patients with active visceral leishmaniasis due to (Ethiopia) and (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from -infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with , may also be involved in the generation of a protective response against and represents a potential vaccine candidate for the control of human leishmaniasis alone, or in combination with other HLA epitopes/antigens.
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http://dx.doi.org/10.3389/fimmu.2017.00750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506215PMC
July 2017

Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis.

Front Immunol 2017 7;8:227. Epub 2017 Mar 7.

Laboratório de Biologia e Bioquímica de Leishmania, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, Brazil; Faculdade de Medicina, Instituto de Investigação em Imunologia, Universidade de São Paulo (USP), São Paulo, Brazil.

Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-γ, IL-1β, and TNF-α and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH and cured subjects. F2 also promoted the highest frequencies of CD3CD4IL-2TNF-αIFN-γ, CD3CD4IL-2TNF-αIFN-γ, CD3CD4IL-2TNF-αIFN-γ, and CD3CD4IL-2TNF-αIFN-γ T cells in cured and asymptomatic subjects. Consistent with this, the IFN-γ increase was correlated with decreased spleen ( = -0.428,  = 0.05) and liver sizes ( = -0.428,  = 0.05) and with increased hematocrit counts ( = 0.532,  = 0.015) in response to F1 domain, and with increased hematocrit ( = 0.512, 0.02) and hemoglobin counts ( = 0.434,  = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 ( = -0.595,  = 0.005) and F2 ( = -0.462,  = 0.04). Conversely, F1 and F3 increased the CD3CD8IL-2TNF-αIFN-γ, CD3CD8IL-2TNF-αIFN-γ, and CD3CD8IL-2TNF-αIFN-γ T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8 T-cell responses against F3 and F1, potentially involved in control of the early infection. The -predicted NH36 epitopes are conserved and bind to many HL-DR and HLA and B allotypes. No human vaccine against is available thus far. In this investigation, we identified the NH36 domains and epitopes that induce CD4 and CD8 T cell responses, which could be used to potentiate a human universal T-epitope vaccine against leishmaniasis.
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http://dx.doi.org/10.3389/fimmu.2017.00227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338038PMC
March 2017

Defective T-lymphocyte migration to muscles in dystrophin-deficient mice.

Am J Pathol 2012 Aug 22;181(2):593-604. Epub 2012 Jun 22.

Laboratory for Innovations in Therapy, Teaching and Bioproducts, Oswaldo Cruz Institute-Fiocruz, Rio de Janeiro, Brazil.

Duchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting 1 in 3500 males, is caused by mutations in the dystrophin gene. DMD leads to degeneration of skeletal and cardiac muscles and to chronic inflammation. The mdx/mdx mouse has been widely used to study DMD; this model mimics most characteristics of the disease, including low numbers of T cells in damaged muscles. In this study, we aimed to assess migration of T cells to the heart and to identify any alterations in adhesion molecules that could possibly modulate this process. In 6-week-old mdx/mdx mice, blood leukocytes, including T cells, were CD62L(+), but by 12 weeks of age down-modulation was evident, with only approximately 40% of T cells retaining this molecule. Our in vitro and in vivo results point to a P2X7-dependent shedding of CD62L (with high levels in the serum), which in 12-week-old mdx/mdx mice reduces blood T cell competence to adhere to cardiac vessels in vitro and to reach cardiac tissue in vivo, even after Trypanosoma cruzi infection, a known inducer of lymphoid myocarditis. In mdx/mdx mice treated with Brilliant Blue G, a P2X7 blocker, these blood lymphocytes retained CD62L and were capable of migrating to the heart. These results provide new insights into the mechanisms of inflammatory infiltration and immune regulation in DMD.
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http://dx.doi.org/10.1016/j.ajpath.2012.04.023DOI Listing
August 2012

Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection.

Am J Pathol 2007 Jul;171(1):79-86

Fundação Oswaldo Cruz/Instituto Oswaldo Cruz, Departamento de Ultra-estrutura e Biologia Celular (DUBC), Laboratório de Biologia Celular, Rio de Janeiro (RJ); Brazil.

Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1941608PMC
http://dx.doi.org/10.2353/ajpath.2007.060643DOI Listing
July 2007
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