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More than just exosomes: distinct Leishmania infantum extracellular products po...

Perez-Cabezas, B; Santarém, N; Cecílio, P; Silva, C; Silvestre, R; A M Catita, J; Cordeiro-da-Silva, A

The use of secretion pathways for effector molecule delivery by microorganisms is a trademark of pathogenesis. Leishmania extracellular vesicles (EVs) were shown to have significant immunomodulatory potential. Still, they will act in conjunction with other released parasite-derived products that might modify the EVs effects. Notwithstanding, the immunomodulatory properties of these non-vesicular components and ...


The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-in...

Laforge, M; Silvestre, R; Rodrigues, V; Garibal, J; Campillo-Gimenez, L; Mouhamad, S; Monceaux, V; Cumont, M; Rabezanahary, H; Pruvost, A

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preser...


L-threonine supplementation during colitis onset delays disease recovery

Gaifem, J; Gonçalves, L; Dinis-Oliveira, R; Cunha, C; Carvalho, A; Torrado, E; Rodrigues, F; Saraiva, M; Castro, A; Silvestre, R

Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most ad...


Response to the comment on "Promising blood-derived biomarkers for estimation o...

Ricardo Jorge Dinis Oliveira; Felix Carvalho; Costa, I; Silvestre, R; Teresa Magalhães

Following Meurs and Szykula's comment on our published article titled "Promising blood-derived biomarkers for estimation of the postmortem interval", we recognize the importance of the issues raised, but we would like to emphasize that these contain some misinterpretations and that most of the points were already discussed in depth in our manuscript particularly in the conclusion section. We also aim to highlig...


AMPK in Pathogens

Mesquita, I; Moreira, D; Sampaio-Marques, B; Laforge, M; Cordeiro-da-Silva, A; Ludovico, P; Estaquier, J; Silvestre, R

During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Amon...


AMP-activated protein kinase as a target for pathogens: Friends or foes?

Moreira, D; Silvestre, R; Cordeiro-da-Silva, A; Estaquier, J; Foretz, M; Viollet, B

Intracellular pathogens are known to manipulate host cell regulatory pathways to establish an optimal environment for their growth and survival. Pathogens employ active mechanisms to hijack host cell metabolism and acquire existing nutrient and energy store. The role of the cellular energy sensor AMP-activated protein kinase (AMPK) in the regulation of cellular energy homeostasis is well documented. Here, we hi...


Interleukin-27 early impacts Leishmania infantum infection in mice and correlat...

Pérez-Cabezas, B; Cecílio, P; Robalo, AL; Silvestre, R; Carrillo, E; Moreno, J; San, Martín J; Vasconcellos, R; Cordeiro-da-Silva, A

The complexity of Leishmania-host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused by Leishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two cla...


Regulation of immunity during visceral Leishmania infection

Rodrigues, V; Cordeiro-da-Silva, A; Laforge, M; Silvestre, R; Estaquier, J

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protecti...


Promising blood-derived biomarkers for estimation of the postmortem interval

Costa, I; Felix Carvalho; Teresa Magalhães; de Pinho, PG; Silvestre, R; Ricardo Jorge Dinis Oliveira

A precise estimation of the postmortem interval (PMI) is one of the most important topics in forensic pathology. However, the PMI estimation is based mainly on the visual observation of cadaverous phenomena (e.g. algor, livor and rigor mortis) and on alternative methods such as thanatochemistry that remain relatively imprecise. The aim of this in vitro study was to evaluate the kinetic alterations of several bi...


Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijac...

Moreira, D; Rodrigues, V; Abengozar, M; Rivas, L; Rial, E; Laforge, M; Li, X; Foretz, M; Viollet, B; Estaquier, J; Cordeiro-da-Silva, A; Silvestre, R

Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection. Nevertheless, little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages. Here, we demonstrate that during L. infantum infection, macrophages switch from an early glycolytic metabolism to an oxidative phosphorylation, a...


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