Assessing the Clinical Impact of the SARS-CoV-2 Gamma Variant on Intensive Care Unit Admissions: Insights from a Reference Hospital in Northeastern Brazil.

The global challenge posed by the prolonged COVID-19 pandemic underscores the critical need for ongoing genomic surveillance to identify emerging variants and formulate effective public health strategies. This retrospective observational study, conducted in a reference hospital in Northeast Brazil and comprising 2116 cases, employed PCR genotyping together with epidemiological data to elucidate the impact of the Gamma variant during its emergence, revealing distinct patterns in hospitalization rates, severity of illness, and outcomes. The study emphasizes the challenges posed by the variant, particularly an increased tendency for ICU admissions and respiratory support, especially among adults aged 18 to 59 without comorbidities. Laboratory analyses further demonstrate elevated inflammatory, coagulation, and hepatic markers in the Gamma variant cohort, suggesting a more severe systemic response. Despite limitations, including a retrospective approach and single-institution data, the study underscores the importance of ongoing genomic surveillance. Overall, this research contributes valuable insights into the impact of the Gamma variant on COVID-19 dynamics, advocating for continued research and surveillance to inform effective public health strategies regarding evolving viral variants.

The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling.

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.

Flavonoid Rutin Presented Anti-Glioblastoma Activity Related to the Modulation of Onco miRNA-125b Expression and STAT3 Signaling and Impact on Microglia Inflammatory Profile.

Glioblastoma (GBM) is the most aggressive and treatment-resistant brain tumor. In the GBM microenvironment, interaction with microglia is associated with the dysregulation of cytokines, chemokines, and miRNAs, contributing to angiogenesis, proliferation, anti-apoptosis, and chemoresistance. The flavonoid rutin can inhibit glioma cell growth associated with microglial activation and production of pro-inflammatory mediators by mechanisms that are still poorly understood. The present study investigated the effect of rutin on viability, regulation of miRNA-125b, and the STAT3 expression in GBM cells, as well as the effects on the modulation of the inflammatory profile and STAT3 expression in microglia during indirect interaction with GBM cells. Human GL15-GBM cells and human C20 microglia were treated or not with rutin for 24 h. Rutin (30-50 µM) significantly reduced the viability of GL15 cells; however, it did not affect the viability of microglia. Rutin (30 µM) significantly reduced the expression of miRNA-125b in the cells and secretome and STAT3 expression. Microglia submitted to the conditioned medium from GBM cells treated with rutin showed reactive morphology associated with reduced expression of IL-6, TNF, and STAT3. These results reiterate the anti-glioma effects of the flavonoid, which may also modulate microglia towards a more responsive anti-tumor phenotype, constituting a promising molecule for adjuvant therapy to GBM.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial.

SARS-CoV-2 and its different variants caused a "wave and wave" pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI - 0.74 [- 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI - 0.28 [0.1-0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

Rapid Detection of SARS-CoV-2 Based on the LAMP Assay Associated with the CRISPRCas12a System.

BACKGROUND: The global public health system has been severely tested by the COVID-19 pandemic. Mass testing was essential in controlling the transmission of the SARS-CoV-2; however, its implementation has encountered challenges, particularly in low-income countries. The urgent need for rapid and accurate tests for SARS-CoV-2 has proven to be extremely important. Point-of-care tests using the CRISPR system for COVID-19 have shown promise, with a reported high sensitivity and rapid detection. The performance of a CRISPR-based SARS-CoV-2 testing system was reported in this study. METHODS: A total of 29 nasopharyngeal samples were evaluated, including 23 samples from individuals suspected of COVID-19, and six samples positive for H3N2 or respiratory syncytial virus. Two reference samples with known concentrations of SARS-CoV-2 RNA (3000 RNA copies/mL) or viral titer determined by plaque assay (105 PFU/mL) were also evaluated. The LAMP technique was employed to amplify the ORF1ab gene and the results were analyzed using a Gemini XPS fluorescence reader. RESULTS: The RT-LAMP-CRISPR/Cas12 assay showed 100% concordance compared to RT-PCR. The RT-PCR presented a detection limit of 0.01 PFU/mL and the CRISPR/Cas12 system showed a limit of 15.6 PFU/mL. The RT-PCR sensitivity was approximately 8 RNA copies/µL and CRISPR/Cas12 at 84 RNA copies/µL. CONCLUSION: The RT-LAMP-CRISPR/Cas12a assay offered a promising alternative for the detection of SARS-CoV-2 and reinforces that CRISPR-based diagnostic techniques can be an alternative for fast and accurate assays.

Cytogenomic Investigation of Syndromic Brazilian Patients with Differences of Sexual Development.

BACKGROUND: Cytogenomic methods have gained space in the clinical investigation of patients with disorders/differences in sexual development (DSD). Here we evaluated the role of the SNP array in achieving a molecular diagnosis in Brazilian patients with syndromic DSD of unknown etiology. METHODS: Twenty-two patients with DSD and syndromic features were included in the study and underwent SNP-array analysis. RESULTS: In two patients, the diagnosis of 46,XX SRY + DSD was established. Additionally, two deletions were revealed (3q29 and Xp22.33), justifying the syndromic phenotype in these patients. Two pathogenic CNVs, a 10q25.3-q26.2 and a 13q33.1 deletion encompassing the FGFR2 and the EFNB2 gene, were associated with genital atypia and syndromic characteristics in two patients with 46,XY DSD. In a third 46,XY DSD patient, we identified a duplication in the 14q11.2-q12 region of 6.5 Mb associated with a deletion in the 21p11.2-q21.3 region of 12.7 Mb. In a 46,XY DSD patient with delayed neuropsychomotor development and congenital cataracts, a 12 Kb deletion on chromosome 10 was found, partially clarifying the syndromic phenotype, but not the genital atypia. CONCLUSIONS: The SNP array is a useful tool for DSD patients, identifying the molecular etiology in 40% (2/5) of patients with 46,XX DSD and 17.6% (3/17) of patients with 46,XY DSD.

Evaluation of 2D and 3D Erythroid Differentiation Protocols Using Sickle Cell Disease and Healthy Donor Induced Pluripotent Stem Cells.

BACKGROUND: Sickle cell disease (SCD) is a highly prevalent genetic disease caused by a point mutation in the HBB gene, which can lead to chronic hemolytic anemia and vaso-occlusive events. Patient-derived induced pluripotent stem cells (iPSCs) hold promise for the development of novel predictive methods for screening drugs with anti-sickling activity. In this study, we evaluated and compared the efficiency of 2D and 3D erythroid differentiation protocols using a healthy control and SCD-iPSCs. METHODS: iPSCs were subjected to hematopoietic progenitor cell (HSPC) induction, erythroid progenitor cell induction, and terminal erythroid maturation. Differentiation efficiency was confirmed by flow cytometry analysis, colony-forming unit (CFU) assay, morphological analyses, and qPCR-based gene expression analyses of HBB and HBG2. RESULTS: Both 2D and 3D differentiation protocols led to the induction of CD34+/CD43+ HSPCs. The 3D protocol showed good efficiency (>50%) and high productivity (45-fold) for HSPC induction and increased the frequency of BFU-E, CFU-E, CFU-GM, and CFU-GEMM colonies. We also produced CD71+/CD235a+ cells (>65%) with a 630-fold cell expansion relative to that at the beginning of the 3D protocol. After erythroid maturation, we observed 95% CD235a+/DRAQ5- enucleated cells, orthochromatic erythroblasts, and increased expression of fetal HBG2 compared to adult HBB. CONCLUSION: A robust 3D protocol for erythroid differentiation was identified using SCD-iPSCs and comparative analyses; however, the maturation step remains challenging and requires further development.

SARS-CoV-2 Detection via RT-PCR in Matched Saliva and Nasopharyngeal Samples Reveals High Concordance in Different Commercial Assays.

BACKGROUND: Self-collected saliva samples can increase the diagnostic efficiency and benefit healthcare workers, patient care, and infection control. This study evaluated the performance of self-collected saliva samples compared to nasopharyngeal swabs using three commercial kits for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Matched nasopharyngeal and saliva samples were collected from 103 patients with either asymptomatic or symptomatic COVID-19. Both samples were evaluated using three commercial kits (TaqCheck, Allplex, and TaqPath). To evaluate sample stability, viral RNA extraction was performed in the presence or absence of an RNA-stabilizing solution. Storage conditions, including the duration, temperature, and stability after freezing and thawing of the samples, were also evaluated. RESULTS: All the saliva samples showed 100% concordance with the nasopharyngeal swab results using TaqCheck and Allplex kits, and 93% using TaqPath kit. No difference was observed in the samples that used the RNA-stabilizing solution compared to the group without the solution. The Ct values of the freeze-thawed samples after 30 days were higher than those on day 0; however, the results were consistent the fresh samples. CONCLUSION: The high concordance of SARS-CoV-2 detection via reverse transcription-polymerase chain reaction (RT-PCR) in matched saliva and nasopharyngeal samples using different commercial assays reinforces the concept that self-collected saliva samples are non-invasive, rapid, and reliable for diagnosing SARS-CoV-2 infection.

The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. METHODS: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). DISCUSSION: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

Immunomodulatory and Anti-fibrotic Effects Following the Infusion of Umbilical Cord Mesenchymal Stromal Cells in a Critically Ill Patient With COVID-19 Presenting Lung Fibrosis: A Case Report.

Background: The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19. Case Presentation: This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 107 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO2/FiO2 ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy. Conclusions: Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation.

SARS-CoV-2 variant of concern P.1 (Gamma) infection in young and middle-aged patients admitted to the intensive care units of a single hospital in Salvador, Northeast Brazil, February 2021.

OBJECTIVES: To evaluate changes in the characteristics of patients with coronavirus disease 2019 (COVID-19) after the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) P.1 (Gamma), by comparing the clinical, demographic, and laboratory profiles of patients hospitalized during the first (May to July 2020) and second (December 2020 to February 2021) pandemic waves. METHODS: Data were collected from the records of COVID-19 patients (n = 4164) admitted to a single hospital in Salvador, Northeast Brazil. SARS-CoV-2 genome sequencing was performed on nasopharyngeal swab samples from 12 patients aged <60 years admitted to the intensive care unit (ICU) in February 2021. RESULTS: Between June 2020 and February 2021, the median age of patients admitted to the ICU decreased from 66 to 58 years (P < 0.05). This was accompanied by an increased proportion of patients without comorbidities (15.32% vs 32.20%, P < 0.0001). A significant reduction in the cycle threshold values of SARS-CoV-2 RT-PCR tests was observed in the second wave (P < 0.0001). Sequencing analysis detected lineage Gamma in all 12 ICU patients sampled in February 2021. CONCLUSIONS: The results of this study demonstrated an increased proportion of younger adults without comorbidities with severe disease during the second COVID-19 wave, shortly after the confirmation of local Gamma circulation.

Is there a place for mesenchymal stromal cell-based therapies in the therapeutic armamentarium against COVID-19?

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs.

Evaluation of urine SARS-COV-2 RT-PCR as a predictor of acute kidney injury and disease severity in patients with critical COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began as an outbreak in Wuhan, China and has spread rapidly across the globe. Although most infections are mild, patients with severe and critical COVID-19 infections face deterioration of respiratory function and may also have extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart, and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material using reverse-transcription polymerase chain reaction in urine samples obtained from patients with COVID-19 receiving critical care. Among 51 included patients, we found higher serum creatinine levels, a longer hospital stay, and more frequent need for dialysis in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.

Early detection of P.1 variant of SARS-CoV-2 in a cluster of cases in Salvador, Brazil.

We report 3 cases of severe COVID-19 due to the SARS-CoV-2 P.1 lineage in a familial cluster detected in Salvador, Bahia-Brazil. All cases were linked to travel by family members from the state of Amazonas to Bahia in late December 2020. This report indicates the cryptic transmission of the SARS-CoV-2 P.1 lineage across Brazil and highlights the importance of genomic surveillance to track the emergence of new SARS-CoV-2 variants of concern.

Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease.

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with T. cruzi and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGFß1) and T. cruzi stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of T. cruzi-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC.

Preclinical validation of occupational and environmental safety of an isolation system for noninvasive ventilation in COVID-19 and other aerosol-transmitted infections.

Background: The current SARS-CoV-2 pandemic has provoked the collapse of some health systems due to insufficient intensive care unit capacity. The use of continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) therapies has been limited in consideration of the risk of occupational infection in health-care professionals. Aims: In preclinical experimental simulations, evaluate occupational and environmental safety of the newly developed isolation system for aerosol-transmitted infections (ISATI). Method: Simulations were conducted to test ISATI's capability to isolate aerosolized molecular (caffeine), and biological (SARS-CoV-2 synthetic RNA) markers. Caffeine deposition was analyzed on nitrocellulose sensor discs by proton nuclear magnetic resonance spectroscopy. Synthetic SARS-CoV-2 detection was performed by reverse transcription-polymerase chain reaction. Results: ISATI demonstrated efficacy in isolating molecular and biological markers within the enclosed environment in simulated conditions of CPAP, HFNO and mechanical ventilation therapy. Neither the molecular marker nor substantial amounts of synthetic SARS-CoV-2 RNA were detected in the surrounding environment, outside ISATI, indicating appropriate occupational safety for health-care professionals. Conclusion: Aerosolized markers were successfully contained within ISATI in all experimental simulations, offering occupational and environmental protection against the dissemination of aerosolized microparticles under CPAP or HFNO therapy conditions, which are indicated for patients with acute respiratory infections.

Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease.

Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease.

Chronic Chagas disease cardiomyopathy (CCC) is the most frequent and severe form of this parasitic disease. CCC is caused by a progressive inflammation in the heart, resulting in alterations that can culminate in heart failure and death. The use of dendritic cells (DCs) appears as an option for the development of treatments due to their important role in regulating immune responses. Here, we investigated whether tolerogenic cells (tDCs) could interfere with the progression of CCC in an experimental model of Chagas disease. The tDCs were generated and characterized as CD11b+ CD11c+ cells, low expression of MHC-II, CD86, CD80, and CD40, and increased expression of PD-L. These cells produced low levels of IL-6 and IL-12p70 and higher levels of IL-10, compared to mature DCs (mDCs). Interestingly, tDCs inhibited lymphoproliferation and markedly increased the population of FoxP3+ Treg cells in vitro, compared to mature DCs. In a mouse model of CCC, treatment with tDCs reduced heart inflammation and fibrosis. Furthermore, tDCs treatment reduced the gene expression of pro-inflammatory cytokines (Ifng and Il12) and of genes related to cardiac remodeling (Col1a2 and Lgals3), while increasing the gene expression of IL-10. Finally, administration of tDCs, increased the percentage of Treg cells in the hearts and spleens of chagasic mice. Ours results show that tolerogenic dendritic cells have therapeutic potential on CCC, inhibiting disease progression.