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
31 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 31
- 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.
- 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.
- 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 vivo Activity of Silver Nanoparticles Against Pseudomonas aeruginosa Infection in Galleria mellonella(2020) THOMAZ, Luciana; ALMEIDA, Luiz Gustavo de; SILVA, Flavia R. O.; CORTEZ, Mauro; TABORDA, Carlos P.; SPIRA, BenyPseudomonas aeruginosa is an opportunistic pathogen associated with life-threatening nosocomial and community-acquired infections. Antibiotic resistance is an immediate threat to public health and demands an urgent action to discovering new antimicrobial agents. One of the best alternatives for pre-clinical tests with animal models is the greater wax moth Galleria mellonella. Here, we evaluated the antipseudomonal activity of silver nanoparticles (AgNPs) against P. aeruginosa strain UCBPP-PA14 using G. mellonella larvae. The AgNPs were synthesized through a non-toxic biogenic process involving microorganism fermentation. The effect of AgNPs was assessed through characterization and quantification of the hemocytic response, nodulation and phenoloxidase cascade. On average, 80% of the larvae infected with P. aeruginosa and prophylactically treated with nanoparticles survived. Both the specific and total larvae hemocyte counts were restored in the treated group. In addition, the nodulation process and the phenoloxidase cascade were less exacerbated when the larvae were exposed to the silver nanoparticles. AgNPs protect the larvae from P. aeruginosa infection by directly killing the bacteria and indirectly by preventing an exacerbated immunological response against the pathogen. Our results suggest that the prophylactic use of AgNPs has a strong protective activity against P. aeruginosa infection.
- Comparison of carpet and toothbrush techniques for the detection ofMicrosporum canis in cats(2020) SANTANA, Aline E.; TABORDA, Carlos P.; FILGUEIRA, Kilder D.; SELLERA, Fabio P.; LARSSON, Carlos E.; RECHE-JUNIOR, ArchivaldoObjectives The aim of this study was to evaluate the diagnostic concordance between the toothbrush and carpet techniques for the detection ofMicrosporum canisin cats in a field study. Methods Thirty-nine Persian cats from a cattery were used. Fungal culture samples from the haircoat of each cat were collected by stroking the coat with a sterile toothbrush and a 5 x 5 cm-sized sterile carpet square (n = 78 total samples). Specimens were inoculated onto Mycosel Agar and incubated at 25 degrees C for 21 days. Both techniques were compared using the following parameters: number of plates without fungal growth, number of plates with contaminant growth and number of plates positive for dermatophytes. Results The feline population in the study cattery was 39. Thirty (77%) were symptomatic and nine (23%) asymptomatic. The diagnosis was made via carpet and toothbrush methods and 78 cultures were performed. On day 21,M caniswas detected in all culture plates. No contaminant molds were observed. Conclusions and relevance The concordance rate between the carpet and toothbrush techniques among the 78 evaluable culture plates was 100%. Both methods are equally effective for collecting material forMcanisculture. Additionally, both techniques are inexpensive and easy to perform in feline clinical practice.
- Differential recognition and cytokine induction by the peptidorhamnomannan from Sporothrix brasiliensis and S. Schenckii(2022) KISCHKEL, Brenda; LOPES-BEZERRA, Leila; TABORDA, Carlos P.; JOOSTEN, Leo A. B.; SANTOS, Jessica C. dos; NETEA, Mihai G.Sporotrichosis is a deep mycosis caused by dimorphic species of the genus Sporothrix, with differences in pathogenicity between S. schenckii and S. brasiliensis species. Recently, it was discovered that the cell wall peptidorhamnomannan (PRM) from S. brasiliensis has additional unknown rhamnose residues. We hypothesize that the structural differences of Sporothrix spp PRMs impact the host's immune response and may explain the severity of sporotrichosis caused by S. brasiliensis. We demonstrate that S. brasiliensis yeasts and its PRM (S.b PRM) induced a strong inflammatory response in human PBMCs, with high production of TNF-alpha, IL-6 and IL-1 beta and induction of T-helper cytokines IFN-gamma, IL-17 and IL-22. In contrast, S. schenckii yeasts and its PRM induced higher concentrations of interleukin-1 receptor antagonist (IL-1Ra), which resulted in low production of T-helper cytokines such as IL-17 and IL-22. CR3 and dectin-1 were required for cytokine induction by both PRMs, while TLR2 and TLR4 were required for the response of S.s PRM and S.b PRM, respectively. IL-1 beta and IL-1 alpha production induced by S. brasiliensis yeasts and S.b PRM were dependent on inflammasome and caspase-1 activation. S. schenckii and S.s PRM were able to induce IL-1 beta independent of ROS. In conclusion, these findings improve our understanding of the pathogenesis of Sporothrix spp. by reporting differences of immunological responses induced by S. schenckii and S. brasiliensis. The study also opens the gateway for novel treatment strategies targeting local inflammation and tissue destruction induced by S. brasiliensis infection through IL-1 inhibition.