Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron

The mechanisms used by Paracoccidioides brasiliensis (Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose-dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocytes and the CHLOR treatment in vitro induces Pb 18 yeast-killing by monocytes by restricting the availability of intracellular iron. Besides, the CHLOR treatment in vivo significantly reduces the number of organisms in the lungs of Pb-infected mice protecting them from several infections. Thus, CHLOR was effective in the treatment of murine paracoccidioidomycosis, suggesting the potential use of this drug in patients' treatment.

Acompanhamento clínico-laboratorial de gatos naturalmente infectados com vírus da imunodeficiência (FIV) tratados com zidovudina(AZT)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Resistência à oxacilina em Staphylococcus aureus provenientes de pacientes do Hospital das Clínicas da Faculdade de Medicina de Botucatu

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ocorrência de microrganismos periodontopatogênicos e viruses herpéticos na cavidade bucal de pacientes portadores de Síndrome de Down

Pós-graduação em Ciência Odontólogica - FOA

Análise imunológica comparada da eficiência e especificidade da hialuronidase recombinante de Polybia paulista (Hymenoptera, Vespidae) expressa em bactéria e levedura

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise proteômica dos alérgenos imunodominantes do veneno da vespa social Polybia paulista

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Pesquisa de Micobacterium Leprae e outras microbactérias em Tatus Selvagens

Pós-graduação em Doenças Tropicais - FMB

Effects of Yersinia enterocolitica O:3 derivatives on B lymphocyte activation in vivo

The potential sequelae of intestinal infection with Yersinia enterocolitica include reactive arthritis, erythema nodosum, Reiter's syndrome and other autoimmune diseases. The role of the immune response in the pathogenesis of these diseases has not been fully defined, but autoimmune manifestations may be a consequence of the increase in autoantibodies as a result of polyclonal B-cell activation induced by Yersinia. We investigated the effects of Y enterocolitica 0:3 derivatives on B lymphocyte activation in vivo. Groups of five specific pathogen free (SPF) Swiss mice were inoculated with bacterial cell extract, Yersinia outermembrane proteins (Yops) or lipopolysaccharide (LPS) obtained from Y enterocolitica 0:3 and their immunoglobulin-secreting spleen cells were detected by isotype-specific protein A plaque assay. The presence of specific anti-Yersinia antibodies and autoantibodies was determined in mouse sera by ELISA. In all experiments a marked increase in the number of secretory cells of different isotypes was observed as early as the third day after inoculation. IgG and IgM anti-Yersinia antibodies were detected in the sera of all inoculated mice, and autoantibodies against myosin in the sera of those inoculated with bacterial cell extract. The sera from animals stimulated with LPS reacted with myelin, actin and laminin, while the sera from mice inoculated with Yops reacted with myelin, thyroglobulin and cardiolipin. These results suggest that SPF Swiss mice inoculated with any one of the Y enterocolitica derivatives tested exhibited polyclonal activation of B lymphocytes as a result of stimulation by various bacterial components and not only LPS stimulation.

Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica 0:8-infected mice

Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms induced by arthritogenic pathogens. In this study we examined the polyclonal activation potential of a virulent strain of Y. enterocolitica serotype O:8 (WA 2707+) and its plasmidless isogenic pair (WA 2707-). SPF Swiss mice were infected intragastrically and spleen cells were obtained on days 7, 14, 21, 28, 35 and 42 after infection. The number of cells secreting nonspecific immunoglobulins of IgG, IgM and IgA isotypes was determined by the ELISPOT technique. The presence of serum-specific antibodies was investigated by ELISA and the presence of autoantibodies by dot-blot assay. Although the patterns of infection of the two bacterial strains were almost the same, only the animals infected with the virulent strain presented clinical anomalies. Neither arthritic nor inflammatory signs were observed in the joints of the infected animals. The greatest activation observed was that of the nonspecific IgM-secreting cells, and their peak of secretion occurred between the 28th and the 42nd day after infection, for both strains of Y. enterocolitica O:8. Only the animals infected with the virulent strain (WA 2707+) produced IgG-specific antibodies in the serum, from the 28th day after infection. The serum of animals infected with either strain showed reactivity to all the autologous constituents tested, mainly on the 28th and 42nd day after infection. It was concluded that infection of mice with either the virulent strain of Y. enterocolitica O:8 or with its plasmidless isogenic pair resulted in the polyclonal activation of the splenic B lymphocytes including some autoreactive clones.

Aggregatibacter actinomycetemcomitans em pacientes com síndrome de down: influência da condição periodontal e higiene bucal

Patients with Down syndrome have varying degrees of mental retardation, physical and motor, and apparently are more susceptible to infectious diseases. Thus, the present study aimed to evaluate the occurrence of Aggregatibacter actinomycetemcomitans in saliva and subgingival biofilms and above of children and adolescents with Down syndrome and analyze the influence of diet, socioeconomic and cultural factors and periodontal condition. After assessing the socio-economic and behavioral, were collected clinical specimens, which were transported to the laboratory of Microbiology and Immunology FOA-UNESP for detection of microorganisms by molecular method and periodontal conditions were evaluated according to the Periodontal Screening Index and Recording. The control group consisted of individuals without the syndrome. The results were analyzed by chi-square test for proportion analysis of variables with three or more categories, or the Mann-Whitney test. The data analysis of this study showed that the occurrence of A. actinomycetemcomitans ranged from 0.0% to 25.0%, both in the group of patients with Down syndrome, as for the control group and this was not affected by socioeconomic characteristics of the target population, either by oral hygiene standards

Fish immunology: the modification and manipulation of the innate immune system: Brazilian studies

The understanding of fish immune system structure and function is essential for the development of new technologies and products to improve productivity. This is the first review on immune system of fish with Brazilian studies. Aquaculture in Brazil has shown massive growth in recent years due to methods of culture intensification. However, these procedures led to disease outbreaks, as well as the chemotherapy and the misuse of antibiotics. A viable alternative to avoid the use of chemicals and prevent economic losses is the administration of immunostimulants and prebiotcs, which act by increasing the innate immune system. In Brazil there is a lack of studies on fish immune system, except by some groups that have studied the effects of the immunostimulants administration in various species.