RESUMO
In this work, we aimed to develop an automatic algorithm for the quantification of total volume and lung impairments in four different diseases. The quantification was completely automatic based upon high resolution computed tomography exams. The algorithm was capable of measuring volume and differentiating pulmonary involvement including inflammatory process and fibrosis, emphysema, and ground-glass opacities. The algorithm classifies the percentage of each pulmonary involvement when compared to the entire lung volume. Our algorithm was applied to four different patients groups: no lung disease patients, patients diagnosed with SARS-CoV-2, patients with chronic obstructive pulmonary disease, and patients with paracoccidioidomycosis. The quantification results were compared with a semi-automatic algorithm previously validated. Results confirmed that the automatic approach has a good agreement with the semi-automatic. Bland-Altman (B&A) demonstrated a low dispersion when comparing total lung volume, and also when comparing each lung impairment individually. Linear regression adjustment achieved an R value of 0.81 when comparing total lung volume between both methods. Our approach provides a reliable quantification process for physicians, thus impairments measurements contributes to support prognostic decisions in important lung diseases including the infection of SARS-CoV-2.
Assuntos
Algoritmos , COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Paracoccidioidomicose/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , COVID-19/fisiopatologia , Feminino , Humanos , Pulmão/fisiopatologia , Medidas de Volume Pulmonar/métodos , Masculino , Pessoa de Meia-Idade , Paracoccidioides/isolamento & purificação , Paracoccidioidomicose/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , SARS-CoV-2/isolamento & purificação , Tomografia Computadorizada por Raios X/métodosRESUMO
The pathogens Schistosoma mansoni and Paracoccidioides brasiliensis share common geographic areas, determining infectious diseases with high mortality rates worldwide. Histopathological and immunological changes induced by each pathogen are well understood; however, the host responses to S. mansoni and P. brasiliensis coinfection are still unknown. Thus, we investigated liver damage and cytokines production in a murine model acutely and chronically coinfected with these pathogens. Fourty male Swiss mice were infected with S. mansoni and P. brasiliensis alone or coinfected. The animals were euthanized with 50 (acute infection) and 120 (chronic infection) days of infection. All infected animals exhibited liver inflammation. Intense granulomatous inflammation was detected in animals infected with S. mansoni alone and those coinfected. Productive and involutive granulomas were clearly observed in acute and chronic infections, respectively. Granuloma size was reduced in the acute phase and increased in the chronic phase of S. mansoni and P. brasiliensis coinfection, compared with animals infected only with S. mansoni. In the chronic phase of infection, the granulomatous inflammation in coinfected animals was characterized by intense neutrophils accumulation and reduced eosinophils number. IFN-γ, IL-2, IL-4, and IL-5 circulating levels were increased in all infected groups. Coinfected animals presented attenuated IFN-γ and IL-4 production in the acute and chronic infections. Taken together, our findings indicate that coinfected animals exhibited a differential modulation of granulomatous inflammation during the acute and chronic phases of infection, which was potentially associated with a divergent profile of cytokines production and migration of neutrophils and eosinophils in response to S. mansoni and P. brasiliensis antigenic stimulation.
Assuntos
Coinfecção , Granuloma , Hepatopatias , Fígado , Paracoccidioides/imunologia , Paracoccidioidomicose , Schistosoma mansoni/imunologia , Esquistossomose mansoni , Animais , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Modelos Animais de Doenças , Granuloma/imunologia , Granuloma/microbiologia , Granuloma/parasitologia , Granuloma/patologia , Fígado/imunologia , Fígado/microbiologia , Fígado/parasitologia , Fígado/patologia , Hepatopatias/imunologia , Hepatopatias/microbiologia , Hepatopatias/parasitologia , Hepatopatias/patologia , Masculino , Camundongos , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/patologia , Paracoccidioidomicose/fisiopatologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/microbiologia , Esquistossomose mansoni/patologiaRESUMO
The Notch signaling pathway participates in several cellular functional aspects. This signaling has an important role in targeting both DC maturation and DC-mediated T cell responses. Thus, it is essential to investigate the influence of this signaling pathway in the role played by DCs in the pathogenesis of experimental paracoccidioidomycosis. This disease is a granulomatous and systemic mycosis that mainly affects lung tissue and can spread to any other organ and system. In this study, we demonstrated that bone marrow-derived DCs infected with yeasts from Paracoccidioides brasiliensis strain 18 performed efficiently their maturation after the activation of Notch signaling, with an increase in CD80, CD86, CCR7, and CD40 expression and the release of cytokines such as IL-6 and TNF-α. We observed that the inhibition of the γ-secretase DAPT impaired the proliferation of T cells induced by DC stimulation. In conclusion, our data suggest that Notch signaling contributes effectively to the maturation of DCs and the DC-mediated activation of the T cell response in P. brasiliensis infections.
Assuntos
Diferenciação Celular , Proliferação de Células , Células Dendríticas/fisiologia , Paracoccidioidomicose/fisiopatologia , Receptores Notch/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Paracoccidioides/crescimento & desenvolvimentoRESUMO
Apoptosis is considered an escape mechanism from the host immune system for the fungus Paracoccidioides spp, and it serves as a vehicle for entry into macrophages without stimulating microbicidal activities. Recently, gp43 of P. brasiliensis was demonstrated to be involved in this process. Therefore, as a new therapeutic alternative, it is very important to study compounds that could reduce the modulation of the induction of apoptosis caused by this fungus. Decyl gallate (G14) is a known antifungal compound, and we decided to investigate its anti-apoptotic properties. Our results demonstrate that G14 was effective against apoptosis induced by gp43, as observed in epithelial cells, and led to a reduction in DNA damage, Bak down-regulation and Bcl-2 up-regulation. Together, these data show that G14 presents promising anti-apoptotic activity.
Assuntos
Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Glicoproteínas/fisiologia , Paracoccidioides/fisiologia , Células A549 , Células Epiteliais Alveolares/microbiologia , Células Epiteliais Alveolares/patologia , Antígenos de Fungos/metabolismo , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/genética , Humanos , Paracoccidioidomicose/fisiopatologia , Proteína Killer-Antagonista Homóloga a bcl-2/genéticaRESUMO
OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial serology and more severe emphysema, stressing the importance of adequate treatment associated with tobacco exposure cessation.
Assuntos
Pulmão/fisiopatologia , Paracoccidioidomicose/fisiopatologia , Adulto , Idoso , Estudos Transversais , Métodos Epidemiológicos , Feminino , Fibrose/microbiologia , Fibrose/patologia , Fibrose/fisiopatologia , Humanos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Paracoccidioidomicose/patologia , Qualidade de Vida , Testes de Função Respiratória , Fumar/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial ...
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pulmão/fisiopatologia , Paracoccidioidomicose/fisiopatologia , Estudos Transversais , Métodos Epidemiológicos , Fibrose/microbiologia , Fibrose/patologia , Fibrose/fisiopatologia , Pulmão/microbiologia , Pulmão/patologia , Consumo de Oxigênio/fisiologia , Paracoccidioidomicose/patologia , Qualidade de Vida , Testes de Função Respiratória , Fumar/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Its major antigen is a 43 kDa glycoprotein whose peptides embody different functions: P10 peptide, a T-cell epitope, induces protective response while P4 and P23 peptides inhibit both, macrophage functions and inflammatory reaction, thus facilitating infection. Here we investigated the modulating mechanisms of the immune response exerted by P4 and P23 involved in the latter inhibitory effect on macrophages. Moreover we analyzed the peptides effects in different models in vivo. While evaluating whether P4 and P23 present systemic anti-inflammatory effects in vivo, we showed that their intraperitonial administration decreased footpad swelling in mice infected with either P. brasiliensis or Mycobacterium bovis. Both, qPCR and ELISA assays suggested that this anti-inflammatory effect depended on alterations in the kinetics of production of innate immunity modulators such as TNF-α, IL6, IL10 and TLR2. IL10 seems to be early produced than TNF-α and IL6, produced later in presence of peptides. Higher doses or intravenously given P4 and P23 resulted in earlier and more prolonged anti-inflammatory effects. Moreover, continuous treatment with P4 and P23 sustained the anti-inflammatory activity throughout.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antígenos de Fungos/química , Proteínas Fúngicas/química , Glicoproteínas/química , Inflamação/tratamento farmacológico , Paracoccidioides/patogenicidade , Paracoccidioidomicose/tratamento farmacológico , Peptídeos/uso terapêutico , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Citocinas/metabolismo , Pé/microbiologia , Inflamação/imunologia , Inflamação/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Paracoccidioides/efeitos dos fármacos , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/fisiopatologia , Peptídeos/síntese química , Peptídeos/química , Peptídeos/farmacologiaRESUMO
Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. The primary pulmonary infection is subclinical in most cases, and individuals may remain infected throughout life without ever developing clinical signs. A small proportion of patients present with clinical disease. The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient's well-being.
Assuntos
Pneumopatias Fúngicas , Paracoccidioides/patogenicidade , Paracoccidioidomicose , Antifúngicos/uso terapêutico , Humanos , América Latina/epidemiologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/fisiopatologia , Paracoccidioides/citologia , Paracoccidioides/imunologia , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/fisiopatologiaRESUMO
Paracoccidioidomycosis is the most prevalent mycosis in Latin America. Although the lungs are the primary site of infection, physicians often see patients because of disseminated disease. Imported paracoccidioidomycosis has been described in different regions of the world in patients who lived in endemic areas. Gastrointestinal disease owing to P. brasiliensis is rarely recognized in life because of nonspecific clinical manifestations. Gastrointestinal disease can present as part of progressive dissemination of infection or as a result of local complications from a silent healing process. This review will summarize the salient features of gastrointestinal paracoccidioidomycosis.
Assuntos
Gastroenteropatias/epidemiologia , Adulto , Antifúngicos/uso terapêutico , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/patogenicidade , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/epidemiologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/fisiopatologiaRESUMO
This study assessed adrenal function in patients with paracoccididioidomycosis who had been treated to determine a possible connection between high antibody titers and adrenal dysfunction attributable to persistence of the fungus in adrenal gland. Adrenal gland function was studied in 28 previously treated patients, 2 (7.1%) of whom were shown to have adrenal insufficiency and 7 (259%) who showed a below normal response to stimuli by adrenocorticotropic hormone. Paracoccidioides brasiliensis was detected in the adrenal gland from one of the patients with adrenal insufficiency. Although the study failed to demonstrate a significant difference between high antibody titers and low cortisol levels, the proportion of adrenal insufficiency detected and the subnormal response to adrenocorticotropic hormone confirmed that adrenal damage is an important sequela of paracoccidioidomycosis. Studies with a larger number of patients should be conducted to confirm the hypothesis of persistence of P. brasiliensis in adrenal gland after therapy.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Insuficiência Adrenal/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Hidrocortisona/toxicidade , Paracoccidioides/efeitos dos fármacos , Paracoccidioidomicose/fisiopatologia , Glândulas Suprarrenais/fisiopatologia , Insuficiência Adrenal/etiologia , Algoritmos , Seguimentos , Humanos , Paracoccidioidomicose/tratamento farmacológicoRESUMO
The gene polymorphisms interferon-gamma (IFN-gamma) +874 T/A and interleukin (IL)-4 -590 C/T have been associated with the altered production of cytokines. Therefore, they might be indicative of the occurrence of Paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis. The analysis of single nucleotide polymorphism (SNP) at position+874 IFN-gamma showed an increase occurrence of A/T genotype in both PCM patients and healthy individuals as control (HIC) (56% and 45%, respectively), while the allelic distribution showed 82% of A allele in the patients and 80% in the controls. The SNP of -590 IL-4 showed that C/T genotype was significantly (p<0.05) more prevalent (39%) in PCM group compared to the HIC group (19%), while IL-4 C/C genotype was significantly less frequent (59%) in the patient group compared to the control group (81%). Otherwise, 41% of PCM patients and 19% of HIC individuals carried the IL-4 T allele. Stimulation of peripheral blood mononuclear cells (PBMC) from PCM patients with cell extract antigenic preparations (PbAg) as well as secreted and surface antigens (MEXO) of P. brasiliensis evidenced that there is no difference in the IFN-gamma production related to A and T alleles between PCM and HIC individuals. However, with IL-4 production, PCM patients classified as C phenotype showed two times more IL-4 production than PCM patients classified as T phenotype and HIC controls. In conclusion, our results suggest that functional genetic variants in the IL-4 promoter could influence the production of IL-4 in PCM.
Assuntos
Interferon gama/genética , Interleucina-4/genética , Paracoccidioidomicose/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Antígenos de Fungos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Predisposição Genética para Doença , Humanos , Imunidade Inata , Interferon gama/metabolismo , Interleucina-4/metabolismo , Masculino , Pessoa de Meia-Idade , Paracoccidioides/imunologia , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: In order to describe the case of an adolescent who developed psoas abscesses caused by Paracoccidiodes brasiliensis. DESCRIPTION: A 12-year-old boy was admitted with a history of daily fever and global lymph nodes enlargement. He had been treated in the last 6 years, with irregular use of the drugs, for an acute form of paracoccidioidomycosis (PCM). He presented a tenderness fluctuating polyadenopathy in all cervical, submandibular, supraclavicular, axillary, and inguinal chains; several lymph nodes were up to 4 cm in diameter, hardened and coalescent. After 1 month of unsuccessful therapy with SMX-TMP, the patient presented a pain in the right groin and difficulty to walk. CT scan showed a global retroperitoneal lymph nodes enlargement, some with central necrosis and two bigger collections adjacent to both psoas muscles. A surgical drainage of the collections was performed for several times. The patient received a total of 1.9 g of Amphotericin B. After 1 month of the last surgical procedure, CT scan showed only a residual collection, and the patient was sent to ambulatory follow-up. We hypothesed that the retroperitoneal lymph nodes became a coalescent mass that fistulized to the psoas compartment. COMMENTS: The patient presented a febrile lymphoproliferative syndrome that is frequently seen in children with PCM. Although a polymorphic manifestation is observed in this disease, psoas abscess is a rare complication of PCM. The health professionals that take care of the patients with PCM must pay attention to the possibility of this one more complication.
Assuntos
Paracoccidioidomicose/complicações , Abscesso do Psoas/etiologia , Adolescente , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Criança , Terapia Diretamente Observada , Febre , Humanos , Infusões Intravenosas , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Linfonodos/diagnóstico por imagem , Masculino , Paracoccidioides/isolamento & purificação , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/fisiopatologia , Cooperação do Paciente , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/tratamento farmacológico , Abscesso do Psoas/cirurgia , Radiografia , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoAssuntos
Interações Hospedeiro-Patógeno , Paracoccidioides , Paracoccidioidomicose , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Paracoccidioides/classificação , Paracoccidioides/genética , Paracoccidioides/patogenicidade , Paracoccidioides/fisiologia , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/fisiopatologiaRESUMO
We review here the advances in the understanding of the immunopathology of human paracoccidioidomycosis (PCM). Its investigation must take in account the intriguing natural history of the mycosis and its agent, providing clues to the mechanisms that lead to development of disease (unbalanced host-parasite relationship?) or to the clinically silent, chronic carrier state (balanced host-parasite relationship?), in exposed people living in endemic areas. Although the literature on this subject has progressed notably, the overall picture of what are the mechanisms of susceptibility or resistance continues to be fragmentary. Major advances were seen in the description of both the cytokines/chemokines associated to the different outcomes of the host-parasite interaction, and the fungus-monocyte/macrophage interaction, and cytokines released thereof by these cells. However, relatively few studies have attempted to modify, even in vitro, the patients' unbalanced immune reactivity. Consequently, the benefits of this improved knowledge did not yet reach clinical practice. Fortunately, the previous notion of the immune system as having two nearly independent arms, the innate and adaptive immunities, leaving a large gap between them, is now being overcome. Immunologists are now trying to dissect the connections between these two arms. This will certainly lead to more productive results. Current investigations should address the innate immunity events that trigger the IL-12/IFN-gamma axis and confer protection against PCM in those individuals living in endemic areas, who have been infected, but did not develop the mycosis.
Assuntos
Interações Hospedeiro-Patógeno , Paracoccidioides/fisiologia , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/fisiopatologia , Citocinas/biossíntese , Citocinas/imunologia , Humanos , Ativação Linfocitária , Macrófagos/imunologia , Paracoccidioides/imunologia , Paracoccidioidomicose/microbiologia , Linfócitos T/imunologiaRESUMO
Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles ("ghosts") can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic dimorphic fungi including Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii. Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs.
Assuntos
Melaninas/metabolismo , Fungos Mitospóricos/patogenicidade , Micoses/microbiologia , Paracoccidioides/patogenicidade , Paracoccidioidomicose/fisiopatologia , Fatores de Virulência/metabolismo , Animais , Humanos , Fungos Mitospóricos/classificação , Fungos Mitospóricos/crescimento & desenvolvimento , Micoses/fisiopatologia , Paracoccidioides/crescimento & desenvolvimento , Paracoccidioides/metabolismo , Paracoccidioidomicose/microbiologia , VirulênciaRESUMO
Alveolar macrophages (AM) are the first host cells to interact with Paracoccidioides brasiliensis (Pb), a primary human pathogen that causes severe pulmonary infections in Latin America. To better understand innate immunity in pulmonary paracoccidioidomycosis, we decided to study the fungicidal and secretory abilities of AM from resistant (A/J) and susceptible (B10.A) mice to infection. Untreated, IFN-gamma and IL-12 primed AM from B10.A and A/J mice were challenged with P. brasiliensis yeasts and cocultured for 72 h. B10.A macrophages presented an efficient fungicidal ability, were easily activated by both cytokines, produced high levels of nitric oxide (NO), IL-12, and MCP-1 associated with low amounts of IL-10 and GM-CSF. In contrast, A/J AM showed impaired cytokine activation and fungal killing, secreted high levels of IL-10 and GM-CSF but low concentrations of NO, IL-12, and MCP-1. The fungicidal ability of B10.A but not of A/J macrophages was diminished by aminoguanidine treatment, although only the neutralization of TGF-beta restored the fungicidal activity of A/J cells. This pattern of macrophage activation resulted in high expression of MHC class II antigens by A/J cells, while B10.A macrophages expressed elevated levels of CD40. Unexpectedly, our results demonstrated that susceptibility to a fungal pathogen can be associated with an efficient innate immunity, while a deficient innate response can ultimately favor the development of a resistant pattern to infection. Moreover, our data suggest that different pathogen recognition receptors are used by resistant and susceptible hosts to interact with P. brasiliensis yeasts, resulting in divergent antigen presentation, acquired immunity, and disease outcomes.
Assuntos
Macrófagos Alveolares/microbiologia , Macrófagos Alveolares/fisiologia , Paracoccidioidomicose/fisiopatologia , Animais , Citocinas/fisiologia , Citometria de Fluxo , Predisposição Genética para Doença , Imunidade Inata , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos , Paracoccidioides/patogenicidade , Paracoccidioidomicose/genética , Paracoccidioidomicose/imunologia , FagocitoseRESUMO
The systemic mycoses like paracoccidioidomycosis and histoplasmosis, are the main cause of adrenal insufficiency in the countries where they arc endemic. In Venezuela an elevated frequency of these mycoses has been registered. The objective of this study was to evaluate the glucocorticoid adrenal function in patients with paracoccidioidomycosis and histoplasmosis hospitalized in the University Hospital "Ruiz y Pácz" of Ciudad Bolivar (Bolivar state) and in the Hospital "Luis Felipe Rojas Guevara", of El Tigre (Anzoátegui state), Venezuela, between January 2003 and January 2004. The test of fast stimulation with synthetic adrenocorticotrophin hormone (ACTH) was applied to a total of 12 patients with diagnosis of some of these mycoses and data of epidemiologic interest were taken. The proportion men:women was of 5:1, the average age was 35.1 +/- 0.37 years, similar to the control group. Basal plasmatic cortisol levels were within the normal rank in all the patients. After the injection of synthetic ACTH, an increase of plasmatic cortisol values in the same rank for patients with a normal adrenal function was observed, but it was significantly lower than the observed for the control group. These results suggest that there is an adrenal gland functional reserve diminution in patients with either Paracoccidioidomycosis or Histoplasmosis. In patients with systemic mycoses, it is important to evaluate the response to the test of fast stimulation with ACTH due to the frequency of impairment of the glucocorticoid adrenal function in our location.
Assuntos
Córtex Suprarrenal/fisiopatologia , Histoplasmose/fisiopatologia , Paracoccidioidomicose/fisiopatologia , Adolescente , Testes de Função do Córtex Suprarrenal , Hormônio Adrenocorticotrópico , Adulto , Idoso , Comorbidade , Doenças Endêmicas , Feminino , Histoplasmose/epidemiologia , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Paracoccidioidomicose/epidemiologia , Venezuela/epidemiologiaRESUMO
In human and experimental paracoccidioidomycosis the severe disease is characterized by depressed cellular immunity whereas the mild disease is associated with persistent T cell immunity. Since the subcutaneous route of antigen inoculation is an efficient inducer of cellular immunity, we decided to study this route of infection and verify its effect on a lethal secondary infection of susceptible hosts. It was observed that the s.c. infection induces positive delayed type hypersensitivity (DTH) responses in 9 different mouse strains, is a self healing process and susceptible mice develop more intense DTH reactions than resistant mice to Paracoccidioides brasiliensis infection. Unexpectedly, the previous s.c. infection of susceptible mice led to immunoprotection or disease exacerbation depending on the route of fungal challenge. Immunoprotection was achieved after intraperitoneal challenge and was associated with persistent cell-mediated immunity and a mixed type-1/type-2 immunity. Exacerbated disease was found after intravenous challenge, was associated with cellular immunity anergy and prevalent type-2 immune response. As a whole, our work demonstrates that susceptibility to P. brasiliensis infection cannot be ascribed to intrinsic inability to mount cellular immune responses, that a single immunization procedure can result in opposite disease outcomes and immunoprotection can be achieved by a balanced Th1/Th2 immunity.
Assuntos
Antígenos de Fungos/administração & dosagem , Paracoccidioides/patogenicidade , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/fisiopatologia , Animais , Anticorpos Antifúngicos/sangue , Antígenos de Fungos/imunologia , Citocinas/metabolismo , Feminino , Hipersensibilidade Tardia , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos , Paracoccidioides/imunologia , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/mortalidade , Células Th1/imunologia , Células Th2/imunologia , Fatores de Tempo , VirulênciaRESUMO
Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies and in many clinical studies, but only in adults. Therefore, the aim of this study was to evaluate adrenal function in children with paracoccidioidomycosis. Twenty-three children with the systemic form of paracoccidioidomycosis were evaluated and divided in two Groups: Group A (n = 8) included children before treatment and Group B (n = 15) children after the end of treatment. Plasma cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium and potassium were measured. They were within normal range in all cases, except for renin activity and aldosterone, which were elevated in some cases. Group A patients showed basal and post-ACTH cortisol levels significantly greater than Group B patients. The results showed that adrenal function was not compromised in these children with paracoccidioidomycosis.
O acometimento adrenal pelo Paracoccidioides brasiliensis é descrito em necropsias e em estudos clínicos, mas apenas em adultos. Portanto, o objetivo deste estudo foi avaliar a função adrenal em crianças com paracoccidioidomicose. Vinte e três crianças com forma sistêmica de paracoccidioidomicose foram avaliadas e divididas em dois grupos: Grupo A (n = 8) pacientes antes de iniciar o tratamento e Grupo B (n = 15) pacientes após o termino do tratamento. Dosagens plasmáticas de cortisol (basal e após teste com ACTH), ACTH, atividade de renina, aldosterona, sódio e potássio foram realizadas. Estas dosagens foram normais em todos os casos, com exceção da atividade da renina e da aldosterona que foram elevadas em alguns casos. Os pacientes do Grupo A mostraram valores de cortisol basal e após-ACTH significativamente maiores que os do Grupo B. Os resultados demonstraram que a função adrenal não foi comprometida neste grupo de crianças com paracoccidioidomicose.