CARLOS PELLESCHI TABORDA
Projetos de Pesquisa
Unidades Organizacionais
BMM, ICB - Docente
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/53 - Laboratório de Micologia, Hospital das Clínicas, Faculdade de Medicina - Líder
55 resultados
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- Intranasal Vaccine Using P10 Peptide Complexed within Chitosan Polymeric Nanoparticles as Experimental Therapy for Paracoccidioidomycosis in Murine Model(2020) SANTOS JUNIOR, Samuel Rodrigues Dos; SILVA, Francenya Kelley Lopes da; DIAS, Lucas Santos; SOUZA, Ana Camila Oliveira; ARAUJO, Marcelo Valdemir de; SILVA, Leandro Buffoni Roque da; TRAVASSOS, Luiz R.; AMARAL, Andre Correa; TABORDA, Carlos P.Paracoccidioidomycosis (PCM) is a granulomatous fungal disease caused by the dimorphic fungal species of Paracoccidioides, which mainly affects the lungs. Modern strategies for the treatment and/or prevention of PCM are based on a Th1-type immune response, which is important for controlling the disease. One of the most studied candidates for a vaccine is the P10 peptide, derived from the 43 kDa glycoprotein of Paracoccidioides brasiliensis. In order to improve its immune modulatory effect, the P10 peptide was associated with a chitosan-conjugated nanoparticle. The nanoparticles presented 220 nm medium size, poly dispersion index (PDI) below 0.5, zeta potential of +20 mV and encapsulation efficiency around 90%. The nanoparticles' non-toxicity was verified by hemolytic test and cell viability using murine macrophages. The nanoparticles were stable and presented physicochemical characteristics desirable for biological applications, reducing the fungal load and the usual standard concentration of the peptide from 4 to 20 times.
- Antibodies Against Glycolipids Enhance Antifungal Activity of Macrophages and Reduce Fungal Burden After Infection with Paracoccidioides brasiliensis(2016) BUENO, Renata A.; THOMAZ, Luciana; MUNOZ, Julian E.; SILVA, Cassia J. da; NOSANCHUK, Joshua D.; PINTO, Marcia R.; TRAVASSOS, Luiz R.; TABORDA, Carlos P.Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs) from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-gamma and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P brasiliensis adding to other well-studied mediators of the immune response to this fungus.
- Serological Diagnosis of Paracoccidioidomycosis: High Rate of Inter-laboratorial Variability among Medical Mycology Reference Centers(2014) VIDAL, Monica Scarpelli Martinelli; NEGRO, Gilda Maria Barbaro Del; VICENTINI, Adriana Pardini; SVIDZINSKI, Teresinha Inez Estivalet; MENDES-GIANNINI, Maria Jose; ALMEIDA, Ana Marisa Fusco; MARTINEZ, Roberto; CAMARGO, Zoilo Pires de; TABORDA, Carlos Pelleschi; BENARD, GilBackground: Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded. Methodology/Principal findings: We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the ""reference'' titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the ""reference'' titers. Titers were transformed into scores: 0 (negative), 1 (healing titers), 2 (active disease, low titers) and 3 (active disease, high titers) according to each center's criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient's treatment. Surprisingly, all centers exhibited a high rate of ""major'' discordances with a mean of 31 (20%) discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better. Conclusion: There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.
- Experimental Therapy of Paracoccidioidomycosis Using P10-Primed Monocyte-Derived Dendritic Cells Isolated From Infected Mice(2019) SILVA, Leandro B. R.; TAIRA, Cleison L.; DIAS, Lucas S.; SOUZA, Ana C. O.; NOSANCHUK, Joshua D.; TRAVASSOS, Luiz R.; TABORDA, Carlos P.Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin American caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Notably, a Th1 immune response is required to control PCM. In this context, dendritic cells (DCs) seem to be essential players in capture, processing and presentation of Paracoccidioides antigens to naive T cells and their further activation. We have previously demonstrated that differentiated DCs from bone marrow cells, pulsed with the immunoprotective peptide 10 (P10), effectively control experimental PCM immunocompetent and immunosuppressed mice. However, this procedure may not be infeasible or it is limited for the therapy of human patients. Therefore, we have sought a less invasive but equally effective approach that would better mimics the autologous transplant of DC in a human patient. Here, we isolated and generated monocyte differentiated dendritic cells (MoDCs) from infected mice, pulsed them with P-10, and used them in the therapy of PCM in syngeneic mice. Similar to the results using BMDCs, the P10-pulsed MoDCs stimulated the proliferation of CD4(+) T lymphocytes, induced a mixed production of Th-1/Th-2 cytokines and decreased the fungal burden in murine lungs in the setting of PCM. The process of differentiating MoDCs derived from an infected host, and subsequently used for therapy of PCM is much simpler than that for obtaining BMDCs, and represents a more reasonable approach to treat patients infected with Paracoccidioides. The results presented suggest that P10-primed MoDC may be a promising strategy to combat complicated PCM as well as to significantly shorten the lengthy requirements for treatment of patients with this fungal disease.
- Vaccines and innmunotherapy against fungi: the new frontier(2013) NOSANCHUK, Joshua D.; TABORDA, Carlos P.
- Editorial: Tropical fungal diseases(2022) TABORDA, Carlos P.; MUNOZ, Julian Esteban; GONZALEZ, Angel
- Vaccine development for pathogenic fungi: current status and future directions(2023) CHECHI, Jessica L.; COSTA, Felipe A. C. da; FIGUEIREDO, Julia M.; SOUZA, Cassia M. de; VALDEZ, Alessandro F.; ZAMITH-MIRANDA, Daniel; CAMARA, Aline C.; TABORDA, Carlos P.; NOSANCHUK, Joshua D.Introduction: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections.Areas covered: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database.Expert opinion: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.
- Proanthocyanidin polymeric tannins from Stryphnodendron adstringens are effective against Candida spp. isolates and for vaginal candidiasis treatment(2018) FREITAS, Aline Luiza Duarte de; KAPLUM, Vanessa; ROSSI, Diego Conrado Pereira; SILVA, Leandro Buffoni Roque da; MELHEM, Marcia de Souza Carvalho; TABORDA, Carlos Pelleschi; MELLO, Joao Carlos Palazzo de; NAKAMURA, Celso Vataru; ISHIDA, KellyEthnopharmacological relevance: The stem bark of Stryphnodendron adstringens (Mart.) Coville is popularly used as anti-inflammatory, astringent and in the treatment of wounds and vaginal infections. Several pharmacological activities have been scientifically proven by in vitro and in vivo experimental assays for antibacterial, antiviral, antiprotozoan, anti-inflammatory and antioxidant. Aim of the study: We investigated whether proanthocyanidin polymeric tannins from the Stryphnodendron adstringens stem bark with antifungal activity against Candida albicans in vitro are also active against planktonic and biofilm cells of Candida non-albicans (CNA, including fluconazole-resistant isolates) and are capable of controlling Candida vaginitis in vivo. Materials and methods: A total of 46 clinical isolates and 5 reference Candida spp. strains were used in this study. The antifungal effects in vitro of tannins (F2 and sub-fraction F2.4) from S. adstringens stem bark were evaluated using a broth microdilution assay (for planktonic yeasts and biofilm dispersion cells) or by XTT assay (for biofilm sessile cells). For in vivo antifungal activity analysis, mice with vaginal infection by C. albicans or C. glabrata were treated with a topical gel containing F2 (alone or combined with oral fluconazole), and the vaginal histopathology and fungal burden (by CFU counts from vaginal homogenates) were analyzed. Results: F2 and F2.4 inhibited the proliferation of planktonic cells of Candida spp., especially that of fluconazoleand/or amphotericin B-resistant isolates. F2 and F2.4 also inhibited the proliferation of Candida biofilm dispersion cells. Moreover, a gel containing F2 efficiently controlled vaginal infection by C. albicans and C. glabrata in mice, with no noticeable toxicity to vaginal tissue. Conclusions: Our data show that proanthocyanidin polymeric tannins obtained from S. adstringens have anti fungal activity in vitro against C. albicans and CNA (including fluconazole-resistant isolates) and presented efficacy in the control of candidiasis in murine model. Therefore, these tannins have potential use in the treatment of vaginal candidiasis, representing interesting alternatives to current antifungals.
- Skin innate immune response against fungal infections and the potential role of trained immunity(2024) BOMBASSARO, Amanda; FIGUEIREDO, Julia Marcondes; TABORDA, Carlos P.; JOOSTEN, Leo A. B.; VICENTE, Vania A.; QUEIROZ-TELLES, Flavio; MEIS, Jacques F.; KISCHKEL, BrendaFungal skin infections are distributed worldwide and can be associated with economic and social traits. The immune response related to skin cells is complex and its understanding is essential to the comprehension of each cell's role and the discovery of treatment alternatives. The first studies of trained immunity (TI) described the ability of monocytes, macrophages and natural killer (NK) cells to develop a memory-like response. However, the duration of TI does not reflect the shorter lifespan of these cells. These conclusions supported later studies showing that TI can be observed in stem and haematopoietic cells and, more recently, also in non-immune skin cells such as fibroblasts, highlighting the importance of resident cells in response to skin disorders. Besides, the participation of less studied proinflammatory cytokines in the skin immune response, such as IL-36 gamma, shed light into a new possibility of inflammatory pathway blockade by drugs. In this review, we will discuss the skin immune response associated with fungal infections, the role of TI in skin and clinical evidence supporting opportunities and challenges of TI and other inflammatory responses in the pathogenesis of fungal skin infections.
- In Vitro Antifungal Activity of LL-37 Analogue Peptides against Candida spp.(2022) PINILLA, Gladys; CORONADO, Yenifer Tatiana; CHAVES, Gabriel; MUNOZ, Liliana; NAVARRETE, Jeannette; SALAZAR, Luz Mary; TABORDA, Carlos Pelleschi; MUNOZ, Julian E.Fungal infections have increased in recent decades with considerable morbidity and mortality, mainly in immunosuppressed or admitted-to-the-ICU patients. The fungal resistance to conventional antifungal treatments has become a public health problem, especially with Candida that presents resistance to several antifungals. Therefore, generating new alternatives of antifungal therapy is fundamental. One of these possibilities is the use of antimicrobial peptides, such as LL-37, which acts on the disruption of the microorganism membrane and promotes immunomodulatory effects in the host. In this study, we evaluated the in vitro antifungal activity of the LL-37 analogue peptides (AC-1, LL37-1, AC-2, and D) against different Candida spp. and clinical isolates obtained from patients with vulvovaginal candidiasis. Our results suggest that the peptides with the best ranges of MICs were LL37-1 and AC-2 (0.07 mu M) against the strains studied. This inhibitory effect was confirmed by analyzing the yeast growth curves that evidenced a significant decrease in the fungal growth after exposure to LL-37 peptides. By the XTT technique we observed a significant reduction in the biofilm formation process when compared to yeasts untreated with the analogue peptides. In conclusion, we suggest that LL-37 analogue peptides may play an important antimicrobial role against Candida spp.