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¿Por qué una célula tumoral es un buen ejemplo de “supervivencia del más apto”? ¿Por qué una célula está constantemente luchando contra la entropía? Acompáñame en este libro a viajar por el maravilloso mundo de la patología. En este primer libro exploraremos la patología básica, comenzando con definiciones, historia, técnicas de laboratorio y continuaremos con la vida y muerte de una célula. Seguiremos con el sistema inmune y sus enfermedades, genética, trastornos hemodinámicos, infecciones y finalmente neoplasias. El trabajo mancomunado entre los profesores de patología y especialistas en áreas tan diversas como fisiología, genética, microbiología, han logrado este resultado. Para explicar cada capítulo, lo hemos pensado en forma de contar una historia para poder guiar el lector. Se hizo uso de un lenguaje claro, con metáforas y ejemplos de la vida diaria para ilustrar y enseñar. Esperamos que este libro sirva a los estudiantes de fisioterapia para tener una comprensión y visión general de la patología y encontrar su pertinencia en su práctica como fisioterapeutas. Por su lenguaje coloquial puede servir como introducción a estudiantes del área de la salud que deseen explorar el área de la patología.

Made available in DSpace on 2022-04-28T19:42:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 The objective was to evaluate meat quality of Rubia Gallega x Nelore (RGN) crossbred compared to Nelore (N) cattle, using mRNA analysis of calpain 1 and 2, calpastatin, myostatin, and TGFβ; and protein abundance profile post mortem based on aged beef of the different genetic groups. Sixteen N and 16 RGN were finished in feedlot by 120 days and harvested. RGN beef presented greater tenderness. Transcripts analysis showed increased levels of TGFβ and MSTN in RGN, indicating differences in muscle fiber formation. However, no difference was observed in mRNA for CAPN1, CAPN2 and CAST. Protein analysis demonstrated increased troponin-T degradation in RGN. Interaction for HSP 27 degradation was observed, indicating the degradation of this protein is faster and greater in RGN than N. No difference in myostatin protein abundance was found. In general, RGN cattle improves beef quality and these differences may be explained by TGFβ and MSTN gene expression, troponin-T degradation and HSP abundance. Faculty of Animal Science and Food Engineering – University of São Paulo USP Faculty of Veterinary Medicine and Animal Science – University of São Paulo USP Faculty of Agricultural and Veterinary Sciences – São Paulo State University UNESP Faculty of Agricultural and Veterinary Sciences – São Paulo State University UNESP

Commensal yeast from the genus Candida is part of the healthy human microbiota. In some cases, Candida spp. dysbiosis can result in candidiasis, the symptoms of which may vary from mild localized rashes to severe disseminated infections. The most prevalent treatments against candidiasis involve fluconazole, itraconazole, miconazole, and caspofungin. Moreover, amphotericin B associated with prolonged azole administration is utilized to control severe cases. Currently, numerous guidelines recommend echinocandins to treat invasive candidiasis. However, resistance to these antifungal drugs has increased dramatically over recent years. Considering this situation, new therapeutic alternatives should be studied to control candidiasis, which has become a major medical concern. Limonene belongs to the group of terpene molecules, known for their pharmacological properties. In this study, we evaluated in vitro the limonene concentration capable of inhibiting the growth of yeast from the genus Candida susceptible or resistant to antifungal drugs and its capacity to induce fungal damage. In addition, intravaginal fungal infection assays using a murine model infected by Candida albicans were carried out and the fungal burden, histopathology, and scanning electron microscopy were evaluated. All of our results suggest that limonene may play a protective role against the infection process by yeast from the genus Candida.

Candida auris and Candida haemulonii complex (C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii) are phylogenetically related species that share some physiological features and habits. In the present study, we compared the virulence of these yeast species using two different experimental models: (i) Galleria mellonella larvae to evaluate the survival rate, fungal burden, histopathology and phagocytosis index and (ii) BALB/c mice to evaluate the survival. In addition, the fungal capacity to form biofilm over an inert surface was analyzed. Our results showed that in both experimental models, the animal survival rate was lower when infected with C. auris strains than the C. haemulonii species complex. The hemocytes of G. mellonella showed a significantly reduced ability to phagocytize the most virulent strains forming the C. haemulonii species complex. Interestingly, for C. auris, it was impossible to measure the phagocytosis index due to a general lysis of the hemocytes. Moreover, it was observed a greater capability of biofilm formation by C. auris compared to C. haemulonii species complex. In conclusion, we observed that C. auris and C. haemulonii complex have different levels of pathogenicity in the experimental models employed in the present study.

BACKGROUND Candida glabrata yeast is the second cause of candidiasis worldwide. Differs from other yeasts since assimilates only glucose and trehalose (a characteristic used in rapid identification tests for this pathogen) by secreting into the medium a highly active acid trehalase encoded by the CgATH1 gene. OBJECTIVE This study aimed to characterise the function of the acid trehalase in the physiopathology of C. glabrata. METHODS Gene deletion was performed to obtain a mutant ath1Δ strain, and the ability of the ath1Δ strain to grow in trehalase, or the presence of trehalase activity in the ath1Δ yeast cells, was verified. We also tested the virulence of the ath1Δ strain in a murine model of infection. FINDINGS The ath1Δ mutant strain grows normally in the presence of glucose, but loses its ability to grow in trehalose. Due to the high acid trehalase activity present in wild-type cells, the cytoplasmic neutral trehalase activity is only detected in the ath1Δ strain. We also observed a significantly lower virulence of the ath1Δ strain in a murine model of infection with either normal or immunocompromised mice. MAIN CONCLUSIONS The acid trehalase is involved in the hydrolysis of external trehalose by C. glabrata, and the enzyme also plays a major virulence role during infectivity.

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries., Author summary Human paracoccidioidomycosis (PCM) represents a serious public health issue due to its disabling sequelae in working-age people and mortality rates (8th among chronic infectious parasitic diseases in endemic countries and first among mycoses in Brazil). Although antifungal drugs have been widely used and provide clinical improvement for patients, the long duration of treatments (commonly from 6 to 12 months) has contributed to non-compliance and worsening of the disease in many cases. Induction of protective immune responses (either prophylactic or immune-therapeutic) remains the most cost-effective approach against most infectious agents. Members of our group have previously reported the protective properties of P10, a peptide contained in Paracoccidioides brasiliensis gp43 antigen, against PCM. However, the magnitude of the CD4+ T-cell responses elicited lacked the capacity of completely protecting experimental animals. We demonstrate here that immunogenic virus-like particles (VLP) carrying multiple copies of P10 peptide substantially improve P10-related cellular immunity in mice. This was particularly true when an adenoviral immunization vector expressed the chimeric VLP. Moreover, VLP/P10 formulations were capable of controlling the host fungal burden and prevented fungal systemic dissemination. The efficacy of diverse VLP/P10 formulations in murine PCM showed at least one promising candidate vaccine against human PCM.

Paracoccidioidomycosis is a systemic granulomatous disease caused by Paracoccidioides spp. A peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4(+) helper-1 immune response in mice and protects against intratracheal challenge with virulent P. brasiliensis. Previously, we evaluated the efficacy of the P10 peptide alone or combined with antifungal drugs in mice immunosuppressed and infected with virulent isolate of P. brasiliensis. In the present work, our data suggest that P10 immunization leads to an effective cellular immune response associated with an enhanced T cell proliferative response. P10-stimulated splenocytes increased nitric oxide (NO) production and induced high levels of IFN-γ, IL-1β and IL-12. Furthermore, significantly increased concentrations of pro-inflammatory cytokines were also observed in lung homogenates of immunized mice. P10 immunization was followed by minimal fibrosis in response to infection. Combined with antifungal drugs, P10 immunization most significantly improved survival of anergic infected mice. Administration of either itraconazole or sulfamethoxazole/trimethoprim together with P10 immunization resulted in 100 % survival up to 200 days post-infection, whereas untreated mice died within 80 days. Hence, our data show that P10 immunization promotes a strong specific immune response even in immunocompromised hosts and thus P10 treatment represents a powerful adjuvant therapy to chemotherapy.

Paracoccidioidomycosis is a granulomatous systemic mycosis endemic in Brazil and other Latin America countries. A DNA vaccine encoding the immunoprotective peptide 10 (P10) significantly reduced the fungal burden in mice when given prior to or after intratracheal challenge with Paracoccidioides brasiliensis. Presently, the generation/expansion of CD4+ CD44hi memory T cells as well as Foxp3+ Treg cells in mice immunized with the DNA vaccine (pcDNA3-P10) before and after infection with P. brasiliensis was investigated. Memory CD4+ CD44hi T cells simultaneously with Foxp3+ Treg cells increased in the spleens and lungs of pcDNA3-P10 immunized mice on day 0, 30, 60 and 120 postinfection. Histopathology of the lung tissue showed minimal inflammation in immunized mice compared with the unimmunized group, suggesting a role for regulatory T cells in controlling the immunopathology. The DNA vaccine shows that the repeated immunization generates memory cells and regulatory T cells that replace the initially protective pro-inflammatory T cells conferring a long term protection while preserving the integrity of the infected tissue.

A phosphorylated peptide, named K40H, derived from the constant region of IgMs was detected in human serum by liquid chromatography coupled to high-resolution mass spectrometry. Synthetic K40H proved to exert a potent in vitro activity against fungal pathogens, and to inhibit HIV-1 replication in vitro and ex vivo. It also showed a therapeutic effect against an experimental infection by Candida albicans in the invertebrate model Galleria mellonella. K40H represents the proof of concept of the innate role that naturally occurring antibody fragments may exert against infectious agents, shedding a new light upon the posthumous role of antibodies and opening a new scenario on the multifaceted functionality of humoral immunity.

In this study, we analyzed the impact of immunization with the peptidorhamnomannan (PRM) from the cell wall of the fungus Scedosporium (Lomentospora) prolificans in a murine model of invasive scedosporiosis. Immunization with PRM decreased the survival of mice infected with S. prolificans. Immunization of mice with PRM led to decreased secretion of pro-inflammatory cytokines and chemokines but did not affect the secretion of IL-10. Mice immunized with PRM showed an increase in IgG1 secretion, which is an immunoglobulin linked to a nonprotective response. Splenocytes isolated from mice infected with S. prolificans and immunized with PRM showed no differences in the percentages of Th17 cells and no increase in the frequency of the CD4(+)CD62L(Low) T cell population. PRM-immunized mice showed a significant increase in the percentage of Treg cells. In summary, our results indicated that immunization with PRM did not assist or improve the immunological response against S. prolificans infection. PRM exacerbated the infection process by reducing the inflammatory response, thereby facilitating colonization, virulence and dissemination by the fungus.

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-γ 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.

Particulate matter, especially PM2.5, is associated with increased morbidity and mortality from respiratory diseases. Studies that focus on the chemical composition of the material are frequent in the literature, but those that characterize the biological fraction are rare. The objectives of this study were to characterize samples collected in Sao Paulo, Brazil on the quantity of fungi and endotoxins associated with PM2.5, correlating with the mass of particulate matter, chemical composition and meteorological parameters. We did that by Principal Component Analysis (PCA) and multiple linear regressions. The results have shown that fungi and endotoxins represent significant portion of PM2.5, reaching average concentrations of 772.23 spores μg −1 of PM2.5 (SD: 400.37) and 5.52 EU mg −1 of PM2.5 (SD: 4.51 EU mg −1 ), respectively. Hyaline basidiospores, Cladosporium and total spore counts were correlated to factor Ba/Ca/Fe/Zn/K/Si of PM2.5 ( p p p p

Background and purpose: The present study reports on the preparation and testing of a sustained delivery system for the immunomodulatory peptide P10 aimed at reducing the in vivo degradation of the peptide and the amount required to elicit a protective immune response against paracoccidioidomycosis.

Paracoccidioides brasiliensis é um fungo dimórfico patogênico agente etiológico da paracoccidioidomicose (PCM), uma micose endêmica no Brasil. A busca por alternativas para reduzir o tempo de tratamento da PCM levou ao desenvolvimento de uma vacina de DNA contendo a sequência do peptídeo P10 de P. brasiliensis. Neste trabalho, avaliamos a geração de células T de memória e células T reguladoras em camundongos imunizados com esta vacina de DNA antes e após o desafio com o fungo, através da análise de seus esplenócitos e linfócitos pulmonares por citometria de fluxo. Os resultados mostram um aumento no percentual de células T reguladoras e de memória no baço e pulmões dos animais imunizados antes e depois de 30, 60 e 120 dias do desafio em comparação com os grupos controle e não imunizado. Outro experimento revelou que o modelo experimental da PCM in vivo é capaz de induzir a expressão de ROR&#947t. Este estudo mostra que nossa vacina de DNA contra a PCM gera células com fenótipo de reguladoras e de memória, caracterizando seu potencial para o tratamento desta micose. Paracoccidioides brasiliensis is a dimorphic fungal pathogen that is the etiological agent of paracoccidioidomycosis (PCM), a mycosis endemic in Brazil. The search for new alternatives to reduce the duration of PCM treatment led to the development of a DNA vaccine encoding the peptide P10 of P. brasiliensis. Presently, we evaluated the generation of memory and regulatory T cells in mice immunized with this DNA vaccine, before and after the challenge with the fungus by analizing their splenocytes and pulmonary lymphocytes by flow cytometry. The results show an increase in the percentage of regulatory and memory T cells on spleens and lungs of immunized mice before and after 30, 60 and 120 days of challenge compared with the control and untreated groups. Another experiment revealed that the PCM in vivo infection model is capable of inducing ROR&#947t expression. This study demonstrates that our DNA vaccine against PCM generates cells with a regulatory and memory phenotype, which shows its potencial in the treatment of this mycosis.

Paracoccidioidomycosis (PCM) is a chronic granulomatous disease that is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. It is endemic in some countries of Latin America and can cause a high-burden fungal infection with significant morbidity and mortality. The peptide P10, which demonstrates immune protection against experimental PCM, was radiolabeled with a radioisotope and evaluated in vivo. The radiolabeling was conducted to trace the pharmacokinetics of the molecule in principal organs and tissues. This was achieved with high radiochemical purity. Biodistribution and scintigraphic imaging showed fast blood clearance that was mainly renal; however, hepatobiliar excretion was also, with marked uptake in cervical lymph nodes. This profile may be useful for the development of a prophylactic drug or vaccine for patients exposed to PCM.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Paracoccidioidomycosis (PCM), a common chronic mycosis in Latin America, is a granulomatous systemic disease caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. the glycoprotein gp43 is the main antigen target of P brasiliensis and a 15-mer internal peptide (QTLIAIHTLAIRYAN), known as P10, defines a major CD4(+)-specific T cell epitope. Previous results have indicated that, besides having a preventive role in conventional immunizations prior to challenge with the fungus, protective anti-fungal effects can be induced in P brasiliensis-infected mice treated with P10 administered with complete Freund's adjuvant (CFA). the peptide elicits an IFN-gamma-dependent Th1 immune response and is the main candidate for effective immunotherapy of patients with PCM, as an adjunctive approach to conventional chemotherapy. in the present study we tested the therapeutic effects of P10 combined with different adjuvants [aluminum hydroxide, CFA, flagellin, and the cationic lipid dioctadecyl-dimethylammonium bromide (DODAB)] in BALB/c mice previously infected with the P brasiliensis Pb18 strain. Significant reductions in the number of colony forming units of the fungus were detected in lungs of mice immunized with P10 associated with the different adjuvants 52 days after infection. Mice treated with DODAB and P10, followed by mice treated with P10 and flagellin, showed the most prominent effects as demonstrated by the lowest numbers of viable yeast cells as well as reductions in granuloma formation and fibrosis. Concomitantly, secretion of IFN-gamma and INF-alpha, in contrast to interleukin (IL)-4 and 11,10, was enhanced in the lungs of mice immunized with P10 in combination with the tested adjuvants, with the best results observed in mice treated with P10 and DODAB. in conclusion, the present results demonstrate that the co-administration of the synthetic P10 peptide with several adjuvants, particularly DODAB, have significant therapeutic effects in experimental PCM. Univ São Paulo, Dept Microbiol, Biomed Sci Inst, BR-05008900 São Paulo, Brazil Univ São Paulo, Sch Pharm, Dept Clin Anal, BR-05008900 São Paulo, Brazil Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil Univ São Paulo, Lab Med Mycol LIM53, IMTSP, BR-05008900 São Paulo, Brazil Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil FAPESP: 11/17267-4 FAPESP: 09/15823-7 FAPESP: 09/53354-9 FAPESP: 07/58750-4 CNPq: 146809/2010-6 Web of Science

Background Antimicrobial peptides are present in animals, plants and microorganisms and play a fundamental role in the innate immune response. Gomesin is a cationic antimicrobial peptide purified from haemocytes of the spider Acanthoscurria gomesiana. It has a broad-spectrum of activity against bacteria, fungi, protozoa and tumour cells. Candida albicans is a commensal yeast that is part of the human microbiota. However, in immunocompromised patients, this fungus may cause skin, mucosal or systemic infections. The typical treatment for this mycosis comprises three major categories of antifungal drugs: polyenes, azoles and echinocandins; however cases of resistance to these drugs are frequently reported. With the emergence of microorganisms that are resistant to conventional antibiotics, the development of alternative treatments for candidiasis is important. In this study, we evaluate the efficacy of gomesin treatment on disseminated and vaginal candidiasis as well as its toxicity and biodistribution. Results Treatment with gomesin effectively reduced Candida albicans in the kidneys, spleen, liver and vagina of infected mice. The biodistribution of gomesin labelled with technetium-99 m showed that the peptide is captured in the kidneys, spleen and liver. Enhanced production of TNF-α, IFN-γ and IL-6 was detected in infected mice treated with gomesin, suggesting an immunomodulatory activity. Moreover, immunosuppressed and C. albicans-infected mice showed an increase in survival after treatment with gomesin and fluconazole. Systemic administration of gomesin was also not toxic to the mic Conclusions Gomesin proved to be effective against experimental Candida albicans infection. It can be used as an alternative therapy for candidiasis, either alone or in combination with fluconazole. Gomesin's mechanism is not fully understood, but we hypothesise that the peptide acts through the permeabilisation of the yeast membrane leading to death and/or releasing the yeast antigens that trigger the host immune response against infection. Therefore, data presented in this study reinforces the potential of gomesin as a therapeutic antifungal agent in both humans and animals.

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients., Author Summary Paracoccidioidomycosis (PCM) is the predominant systemic mycosis in Latin America causing half of the total deaths among systemic fungal infectious diseases in Brazil. Chemotherapy is the standard treatment, but the long time required, severe cases of immunosuppression and frequent relapses indicate that additional methods should be introduced such as immunotherapy combined with antifungal drugs. Previously, the protective activity of P10, a peptide derived from the major diagnostic antigen gp43, was demonstrated, alone or combined with chemotherapy. P10 elicited a vigorous IFN-γ mediated Th-1 immune response. Presently, the reduction of fungal load, and even sterilization, was attempted using a specific DNA vaccine encoding P10. Plasmid pcDNA3 expression vector with P10 insert was tested as a vaccine in intratracheally infected BALB/c and B10.A mice. Our results showed that vaccination with pP10 induced a significant reduction of the fungal burden in the lung. Co-vaccination of pP10 with a plasmid encoding mouse IL-12 proved to be even more effective in the elimination of the fungus with virtual sterilization in a long term infection and treatment assay system. The data suggest that immunization with these plasmids, without the need of an adjuvant, could be used in the prevention and treatment of PCM in human patients.

The present study reports on the preparation and testing of a sustained delivery system for the immunomodulatory peptide P10 aimed at reducing the in vivo degradation of the peptide and the amount required to elicit a protective immune response against paracoccidioidomycosis.BALB/c mice were infected with the yeast Paracoccidioides brasiliensis to mimic the chronic form of paracoccidioidomycosis. The animals were treated daily with sulfamethoxazole/trimethoprim alone or combined with peptide P10, either emulsified in Freund's adjuvant or entrapped in poly(lactic acid-glycolic acid) (PLGA) nanoparticles at different concentrations (1 microg, 5 microg, 10 microg, 20 microg or 40 microg.50 microL(-1)). Therapeutic efficacy was assessed as fungal burden in tissues and the immune response by quantitative determination of cytokines.Animals given combined chemotherapy and P10 nanotherapy presented a marked reduction of fungal load in the lungs, compared with the non-treated animals. After 30 days of treatment, P10 entrapped within PLGA (1 microg.50 microL(-1)) was more effective than 'free' P10 emulsified in Freund's adjuvant (20 microg.50 microL(-1)), as an adjuvant to chemotherapy. After treatment for 90 days, the higher doses of P10 entrapped within PLGA (5 or 10 microg.50 microL(-1)) were most effective. Treatment with P10 emulsified in Freund's adjuvant (20 microg.50 microL(-1)) or P10 entrapped within PLGA (1 microg.50 microL(-1)) were accompanied by high levels of interferon-gamma in lung.Combination of sulfamethoxazole/trimethoprim with the P10 peptide entrapped within PLGA demonstrated increased therapeutic efficacy against paracoccidioidomycosis. P10 incorporation into PLGA nanoparticles dramatically reduced the peptide amount necessary to elicit a protective effect.

The protective role of specific antibodies againstParacoccidioides brasiliensisis controversial. In the present study, we analyzed the effects of monoclonal antibodies on the major diagnostic antigen (gp43) using in vitro and in vivoP. brasiliensisinfection models. The passive administration of some monoclonal antibodies (MAbs) before and after intratracheal or intravenous infections led to a reduced fungal burden and decreased pulmonary inflammation. The protection mediated by MAb 3E, the most efficient MAb in the reduction of fungal burden, was associated with the enhanced phagocytosis ofP. brasiliensisyeast cells by J774.16, MH-S, or primary macrophages. The ingestion of opsonized yeast cells led to an increase in NO production by macrophages. Passive immunization with MAb 3E induced enhanced levels of gamma interferon in the lungs of infected mice. The reactivity of MAb 3E against a panel of gp43-derived peptides suggested that the sequence NHVRIPIGWAV contains the binding epitope. The present work shows that some but not all MAbs against gp43 can reduce the fungal burden and identifies a new peptide candidate for vaccine development.