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Increased hepatic iron in mice lacking classical MHC class I molecules.

Cardoso, Elsa M.; Macedo, Maria G.; Rohrlich, Pierre; Ribeiro, Eduarda; Silva, Manuel T.; Lemonnier, François A.; de Sousa, Maria

Iron accumulation in the liver in hereditary hemochromatosis (HH) has been shown to be highly variable. Some studies point to the importance of major histocompatibility complex (MHC) class I (MHC-I) and CD8(+) cells as modifiers of iron overload. In this report, using mice knockout for H2K(b-/-) and H2D(b-/-) genes, it is demonstrated that lack of classical MHC-I molecules results in a spontaneous increase of n...


Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolacton...

Gama, José B.; Ohlmeier, S.; Martins, Teresa G.; Fraga, Alexandra G.; Marques, Belém Sampaio; Carvalho, M. Alice; Proença, M. Fernanda R. P.

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms ...


Neutrophils and macrophages: the main partners of phagocyte cell systems

Silva, Manuel T.; Neves, Margarida Correia

Biological cellular systems are groups of cells sharing a set of characteristics, mainly key function and origin. Phagocytes are crucial in the host defense against microbial infection. The previously proposed phagocyte cell systems including the most recent and presently prevailing one, the mononuclear phagocyte system (MPS), grouped mononuclear cells but excluded neutrophils, creating an unacceptable situatio...


Local and regional re-establishment of cellular immunity during curative antibi...

Martins, Teresa G.; Gama, José B.; Fraga, Alexandra G.; Saraiva, Margarida; Silva, Manuel T.; Castro, António G.; Pedrosa, Jorge

BACKGROUND: Buruli ulcer (BU) is a neglected necrotizing disease of the skin, subcutaneous tissue and bone, caused by Mycobacterium ulcerans. BU pathogenesis is associated with mycolactone, a lipidic exotoxin with cytotoxic and immunosuppressive properties. Since 2004, the World Health Organization recommends the treatment of BU with a combination of rifampicin and streptomycin (RS). Histological analysis of hu...


Cellular immunity confers transient protection in experimental buruli ulcer fol...

Fraga, Alexandra G.; Martins, Teresa G.; Torrado, Egídio; Huygen, Kris; Portaels, Françoise; Silva, Manuel T.; Castro, António G.; Pedrosa, Jorge

BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better prevent...


Corticosteroid-Induced Immunosuppression ultimately does not compromise the eff...

Martins, Teresa G.; Trigo, Gabriela; Fraga, Alexandra G.; Gama, José B.; Longatto Filho, Adhemar; Saraiva, Margarida; Silva, Manuel T.

Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathologi...


The bacterial exotoxin AIP56 induces fish macrophage and neutrophil apoptosis u...

Ramos, Carolina Costa; Vale, Ana do; Ludovico, Paula; Santos, Nuno M. S.; Silva, Manuel T.

It has been previously shown that the exotoxin of the important fish pathogen Photobacterium damselae ssp. piscicida is a key pathogenicity factor and is responsible for the extensive systemic apoptosis of macrophages and neutrophils seen in acute fish photobacteriosis. The focus of the present study was to further characterize the AIP56-induced apoptosis of sea bass professional phagocytes by assessing the inv...


Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional ...

Fraga, Alexandra G.; Cruz, Andrea; Martins, Teresa G.; Torrado, Egídio; Saraiva, Margarida; Pereira, Daniela Maria Ramos; Meyers, Wayne M.

Buruli ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans, characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity, M. ulcerans infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific IFN-...


Pathogenetic mechanisms of the intracellular parasite Mycobacterium ulcerans le...

Silva, Manuel T.; Portaels, Françoise; Pedrosa, Jorge

The necrotising skin infection Buruli ulcer is at present the third most common human mycobacteriosis worldwide, after tuberculosis and leprosy. Buruli ulcer is an emergent disease that is predominantly found in humid tropical regions. There is no vaccine against Buruli ulcer and its treatment is diffi cult. In addition to the huge social eff ect, Buruli ulcer is of great scientifi c interest because of the uni...


First cultivation and characterization of mycobacterium ulcerans from the envir...

Portaels, Françoise; Meyers, Wayne M.; Ablordey, Anthony; Castro, António G.; Chemlal, Karim; Rijk, Pim de; Elsen, Pierre; Fissette, Krista

Background: Mycobacterium ulcerans disease, or Buruli ulcer (BU), is an indolent, necrotizing infection of skin, subcutaneous tissue and, occasionally, bones. It is the third most common human mycobacteriosis worldwide, after tuberculosis and leprosy. There is evidence that M. ulcerans is an environmental pathogen transmitted to humans from aquatic niches; however, well-characterized pure cultures of M. ulceran...


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