Cytotoxic T cells and mycobacteria

How the immune system kills Mycobacterium tuberculosis is still a puzzle. the classical picture of killing due to phagocytosis by activated macrophages may be only partly correct. Based on recent evidence, we express here the view that cytotoxic T lymphocytes also make an important contribution and suggest that DNA vaccines might be a good way to enhance this. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.Univ São Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Bromatol & Toxicol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilWeb of Scienc

Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells

This study aimed to demonstrate that microspheres, used as delivery vehicle of DNA-Hsp65/TDM [plasmid DNA encoding heat shock protein 65 (Hsp65) coencapsulated with trehalose dimycolate (TDM) into PLGA microspheres], are widely spread among several organs after intramuscular administration in BALB/c mice. In general, we showed that these particles were phagocytosed by antigen presenting cells, such as macrophages and dendritic cells. Besides, it was demonstrated herein that draining lymph node cells presented a significant increase in the number of cells expressing costimulatory molecules (CD80 and CD86) and MHC class II, and also that the administration of the DNA-Hsp65/TDM and vector/TDM formulations resulted in the up-regulation of CD80, CD86 and MHC class II expression when compared to control formulations (vector/TDM and empty). Regarding the intracellular trafficking we observed that following phagocytosis, the microspheres were not found in the late endosomes and/or lysosomes, until 15 days after internalization, and we suggest that these constructions were hydrolysed in early compartments. Overall, these data expand our knowledge on PLGA [poly (lactic-co- glycolic acid)] microspheres as gene carriers in vaccination strategies, as well as open perspectives for their potential use in clinical practice

A new “Bat-Voiced” species of Dendropsophus Fitzinger, 1843 (Anura, Hylidae) from the Amazon Basin, Brazil

We describe Dendropsophus ozzyi sp. nov., a new species of treefrog, tentatively included in the Dendropsophus microcephalus Group and most notably diagnosed by the presence of pointed fingers and an advertisement call with a very high dominant frequency. The new species is known from three localities in the Brazilian Amazon forest, two on western State of Pará and one (the type locality) in eastern State of Amazonas (03°56’50”S and 58°26’36”W, 45 m a.s.l.).Fil: Orrico, Victor G. D.. Universidade Estadual de Santa Cruz; BrasilFil: Peloso, Pedro L. V.. American Museum Of Natural History; Estados Unidos. Museu Paraense Emílio Goeldi; BrasilFil: Sturaro, Marcelo J.. Museu Paraense Emílio Goeldi; Brasil. Universidade Federal Do Pará; BrasilFil: Silva Filho, Heriberto F. Da. Universidade Federal Do Pará; BrasilFil: Neckel Oliveira, Selvino. Universidade Federal Da Santa Catarina; BrasilFil: Gordo, Marcelo. Universidade Federal do Amazonas; BrasilFil: Faivovich, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Haddad, Celio F. B.. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi

A Dynamic Analysis of Tuberculosis Dissemination to Improve Control and Surveillance

Background: Detailed analysis of the dynamic interactions among biological, environmental, social, and economic factors that favour the spread of certain diseases is extremely useful for designing effective control strategies. Diseases like tuberculosis that kills somebody every 15 seconds in the world, require methods that take into account the disease dynamics to design truly efficient control and surveillance strategies. The usual and well established statistical approaches provide insights into the cause-effect relationships that favour disease transmission but they only estimate risk areas, spatial or temporal trends. Here we introduce a novel approach that allows figuring out the dynamical behaviour of the disease spreading. This information can subsequently be used to validate mathematical models of the dissemination process from which the underlying mechanisms that are responsible for this spreading could be inferred. Methodology/Principal Findings: The method presented here is based on the analysis of the spread of tuberculosis in a Brazilian endemic city during five consecutive years. The detailed analysis of the spatio-temporal correlation of the yearly geo-referenced data, using different characteristic times of the disease evolution, allowed us to trace the temporal path of the aetiological agent, to locate the sources of infection, and to characterize the dynamics of disease spreading. Consequently, the method also allowed for the identification of socio-economic factors that influence the process. Conclusions/Significance: The information obtained can contribute to more effective budget allocation, drug distribution and recruitment of human skilled resources, as well as guiding the design of vaccination programs. We propose that this novel strategy can also be applied to the evaluation of other diseases as well as other social processes.Instituto do Milenio REDE-TBConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)[0012-05.03/04]Fundacao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)[0203-1.05/08

Study of the Technical Feasibility of the Use of Polypropylene Residue in Composites for Automotive Industry

Polypropylene (PP) is widely used in short-term use artifacts, rapidly discarded and should partially replace neat PP. In addition, it is one of the polymers most used in the automobile industry. This study shows the technical feasibility of partially substituting neat PP for a post-consumer counterpart (PPr), as well as adding ground glass (GP), used as filler in the polymer matrix. Mechanical and thermal properties of the recycled blends (PP/PPr) and composites (PP/PPr/GP) were evaluated. The results demonstrated that the blend with the highest PPr content obtained a statistically significant decline in elastic modulus, but adding 5 wt% of GP to this blend increased this property, achieving a similar value in relation to neat PP. The composite developed may be a promising tailor-made product with properties resembling those of the virgin plastic. Thus, the automotive industry seems to be a good option for the use of PPr and GP composites and blends, without increasing product requirements

Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages

Abstract\ud \ud Background\ud Phospholipases C (PLCs) are virulence factors found in several bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE2, an essential factor in cell membrane protection.\ud \ud \ud Results\ud Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE2 production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE2 inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE2 production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.\ud \ud \ud Conclusions\ud \ud Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE2 production.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant No. 2009/07169-5), and PAA was an FAPESP fellowship recipient (Grant No. 2011/01845-9)