LUDMILA RODRIGUES PINTO FERREIRA CAMARGO
Projetos de Pesquisa
Unidades Organizacionais
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells(2017) LAVINI-RAMOS, Carolina; SILVA, Hernandez Moura; SOARES-SCHANOSKI, Alessandra; MONTEIRO, Sandra Maria; FERREIRA, Ludmila Rodrigues Pinto; PACANARO, Ana Paula; GOMES, Samirah; BATISTA, Janaina; FAE, Kellen; KALIL, Jorge; COELHO, VeronicaThe mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-gamma and TNF-alpha production, along IL-10 increase, (ii) CD73(+) Foxp3(+) Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an integrating molecule for both AdMSC and T cells in molecular networks built with our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition significantly decreased AdMSC suppressive effect, confirming their important role in suppressive acitivity. We conclude that MMP9 and 2 are robust new players involved in human MSC immunoregulatory mechanisms, and the higher suppressive activity correlates to their capacity to trigger a coordinated action of multiple specific molecules, mobilizing various immunoregulatory mechanisms.
- The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi(2016) ERSCHING, Jonatan; VASCONCELOS, Jose R.; FERREIRA, Camila P.; CAETANO, Braulia C.; MACHADO, Alexandre V.; BRUNA-ROMERO, Oscar; BARON, Monique A.; FERREIRA, Ludmila R. P.; CUNHA-NETO, Edecio; ROCK, Kenneth L.; GAZZINELLI, Ricardo T.; RODRIGUES, Maurcio M.The beta 1i, beta 2i and beta 5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease), immunity to which is dependent on CD8(+) T cells and IFN-gamma (the classical immunoproteasome inducer). We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruziinfected beta 1i, beta 2i and beta 5i triple knockout (TKO) mice presented significantly lower frequencies and numbers of splenic CD8(+) effector T cells (CD8(+) CD44(high)CD62L(low)) specific for the previously characterized immunodominant (VNHRFTLV) H-2K(b)-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8(+) T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-gamma(+)/TNF+) or single-positive (IFN-gamma(+)) cells specific for the H-2K(b)-restricted immunodominant as well as subdominant T. cruzi epitopes were higher inWT mice, whereas TNF single-positive cells prevailed among CD8(+) T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8(+) T cell responses.
- Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-gamma and CD40-CD40L Interactions(2014) ABEL, Lucia Cristina Jamli; FERREIRA, Ludmila Rodrigues Pinto; NAVARRO, Isabela Cunha; BARON, Monique Andrade; KALIL, Jorge; GAZZINELLI, Ricardo Tostes; RIZZO, Luiz Vicente; CUNHA-NETO, EdecioChagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-gamma secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-gamma primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-gamma. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins.
- Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction (vol 215, pg 387, 2017)(2020) FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; NAKAYA, Helder Imoto; DENG, Xutao; CANDIDO, Darlan da Silva; OLIVEIRA, Lea Campos de; BILLAUD, Jean-Noel; LANTERI, Marion C.; RIGAUD, Vagner Oliveira-Carvalho; SEIELSTAD, Mark; KALIL, Jorge; FERNANDES, Fabio; RIBEIRO, Antonio Luiz Pinho; SABINO, Ester Cerdeira; CUNHA-NETO, Edecio
- Integration of miRNA and gene expression profiles suggest a role for miRNAs in the pathobiological processes of acute Trypanosoma cruzi infection(2017) FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; LAUGIER, Laurie; CABANTOUS, Sandrine; NAVARRO, Isabela Cunha; CANDIDO, Darlan da Silva; RIGAUD, Vagner Carvalho; REAL, Juliana Monte; PEREIRA, Glaucia Vilar; PEREIRA, Isabela Resende; RUIVO, Leonardo; PANDEY, Ramendra Pati; SAVOIA, Marilda; KALIL, Jorge; LANNES-VIEIRA, Joseli; NAKAYA, Helder; CHEVILLARD, Christophe; CUNHA-NETO, EdecioChagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America. Its acute phase is associated with high parasitism, myocarditis and profound myocardial gene expression changes. A chronic phase ensues where 30% develop severe heart lesions. Mouse models of T. cruzi infection have been used to study heart damage in Chagas disease. The aim of this study was to provide an interactome between miRNAs and their targetome in Chagas heart disease by integrating gene and microRNA expression profiling data from hearts of T. cruzi infected mice. Gene expression profiling revealed enrichment in biological processes and pathways associated with immune response and metabolism. Pathways, functional and upstream regulator analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs revealed enrichment in biological processes and pathways such as IFN gamma, TNF alpha, NF-kappa B signaling signatures, CTL-mediated apoptosis, mitochondrial dysfunction, and Nrf2-modulated antioxidative responses. We also observed enrichment in other key heart disease-related processes like myocarditis, fibrosis, hypertrophy and arrhythmia. Our correlation study suggests that miRNAs may be implicated in the pathophysiological processes taking place the hearts of acutely T. cruzi-infected mice.
- Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction(2017) FERREIRA, Ludmila Rodrigues Pinto; FERREIRA, Frederico Moraes; NAKAYA, Helder Imoto; DENG, Xutao; CNDIDO, Darlan da Silva; OLIVEIRA, Lea Campos de; BILLAUD, Jean-Noel; LANTERI, Marion C.; RIGAUD, Vagner Oliveira-Carvalho; SEIELSTAD, Mark; KALIL, Jorge; FERNANDES, Fabio; RIBEIRO, Antonio Luiz P.; SABINO, Ester Cerdeira; CUNHA-NETO, EdecioChagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8(+) T-cell cytotoxicity, separated the 2 groups. NK/CD8(+) T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.