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- Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen SpeciesPublication . Vale-Costa, Sílvia; Gomes Pereira, Sandra Isabel; Teixeira, Carlos Miguel; Rosa, Gustavo; Rodrigues, Pedro Nuno; Tomás, Ana; Appelberg, Rui; Gomes, Maria SaloméIron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host’s iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host’s oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs.
- Avaliação de riscos biológicos e implementação do plano de ação em laboratórios BSL3Publication . Neto, Flávio; Gomes Pereira, Sandra Isabel; Neto, Hernâni VelosoBiological risk assessment is an essential tool to trigger and develop appropriate protective measures, which are determined by the characteristics of the agents involved in the activity and by the adequacy of the facilities, equipment and work practices. The main purpose of this work was to evaluate and manage biological risks in biosafety level 3 (BSL3) facilities, as well the risk assessment and categorization in the activities developed in a research laboratory. The method selected was the MARAT (method of risk assessment and work accidents) and the biological agent under evaluation was Mycobacterium tuberculosis (Mtb), the bacteria responsible for human tuberculosis. The BSL3 laboratory and the research procedures were evaluated concerning the infrastructure (including equipment) and laboratory organization, good laboratory practice, decontamination procedures, emergency procedures in case of an incident /laboratory accident and transport of biological samples. The assessment study of biological risks and the development of an action plan in BSL3 contributes to the development of risk management and guarantees the safety and health of the workers exposed in these laboratories.
- Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient micePublication . Gomes Pereira, Sandra Isabel; Rodrigues, Pedro Nuno; Appelberg, Rui; Gomes, Maria SaloméMycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta 2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta 2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection.