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Broad spectrum immunomodulatory effects of Anopheles gambiae microRNAs and their use for transgenic suppression of Plasmodium Institute of Tropical Medicine

Shengzhang Dong, Xiaonan Fu, Yuemei Dong, Maria Luisa Simoes, Jinsong Zhu, George Dimopoulos

Malaria, caused by the protozoan parasite Plasmodium and transmitted by Anopheles mosquitoes, represents a major threat to human health. Plasmodium's infection cycle in the Anopheles vector is critical for transmission of the parasite between humans. The midgut-stage bottleneck of infection is largely imposed by the mosquito's innate immune system. microRNAs (miRNAs, small noncoding RNAs that bind to target RNAs to regulate gene expression) ...

Potential of lichen secondary metabolites against Plasmodium liver stage parasites with FAS-II as the potential target KU Leuven University of Antwerp

Duc Hung Pham, Camila Esguerra
Chemicals targeting the liver stage (LS) of the malaria parasite are useful for causal prophylaxis of malaria. In this study, four lichen metabolites, evernic acid (1), vulpic acid (2), psoromic acid (3), and (+)-usnic acid (4), were evaluated against LS parasites of Plasmodium berghei. Inhibition of P. falciparum blood stage (BS) parasites was also assessed to determine stage specificity. Compound 4 displayed the highest LS activity and stage ...

Experimental malaria-associated acute respiratory distress syndrome is dependent on the parasite-host combination and coincides with normocyte invasion Institute of Tropical Medicine KU Leuven

Leen Vandermosten, Thy, Hendrik Possemiers, Sofie Knoops, Evelien Van Herck, Julie Deckers, Blandine Franke-Fayard, Tracey J Lamb, Chris J Janse, Ghislain Opdenakker, et al.

BACKGROUND: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a complication of malaria with a lethality rate of up to 80% despite anti-malarial treatment. It is characterized by a vast infiltration of leukocytes, microhaemorrhages and vasogenic oedema in the lungs. Previously, a mouse model for MA-ARDS was developed by infection of C57BL/6 mice with the Edinburgh line NK65-E of Plasmodium berghei.

RESULTS: Here, ...

von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome Institute of Tropical Medicine KU Leuven

Sirima Kraisin, Sebastien Verhenne, Thy, Kimberly Martinod, Claudia Tersteeg, Nele Vandeputte, Hans Deckmyn, Karen Vanhoorelbeke, Philippe E. Van den Steen, Simon F De Meyer, et al.

Background: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a lethal complication of severe malaria, characterized by marked pulmonary inflammation. Patient studies have suggested a link between von Willebrand factor (VWF) and malaria severity.

Objectives: To investigate the role of VWF in the pathogenesis of experimental MA-ARDS.

Methods: Plasmodium berghei NK65-E (PbNK65) parasites were injected in Vwf+/+ ...

Skeleton binding protein-1-mediated parasite sequestration inhibits spontaneous resolution of malaria-associated acute respiratory distress syndrome Institute of Tropical Medicine KU Leuven

Hendrik Possemiers, Thy, Marion Coens, Emilie Pollenus, Sofie Knoops, Sam Noppen, Leen Vandermosten, Sigrid D'haese, Luna Dillemans, Fran Prenen, et al.

Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental ...

Adrenal hormones mediate disease tolerance in malaria Institute of Tropical Medicine KU Leuven Ghent University Flanders Institute for Biotechnology

Leen Vandermosten, Thy, Sofie Knoops, Charlotte De Geest, Natacha Lays, Kristof Van der Molen, Christopher J Kenyon, Manu Verma, Karen E Chapman, Frans Schuit, et al.

Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by ...

Pathogenic CD8+ T cells cause increased levels of VEGF-A in experimental malaria-associated acute respiratory distress syndrome, but therapeutic VEGFR inhibition is not effective Institute of Tropical Medicine KU Leuven

Thy, Melissa Verheijen, Leen Vandermosten, Katrien Deroost, Sofie Knoops, Kathleen Van den Eynde, Louis Boon, Chris J Janse, Ghislain Opdenakker, Philippe E. Van den Steen, et al.

Malaria is a severe disease and kills over 400,000 people each year. Malarial complications are the main cause of death and include cerebral malaria and malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite antimalarial treatment, lethality rates of MA-ARDS are still between 20 and 80%. Patients develop pulmonary edema with hemorrhages and leukocyte extravasation in the lungs. The vascular endothelial growth factor-A ...

Immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome KU Leuven

Philippe Van den Steen, Nathalie Geurts, Katrien Deroost, Sebastien Verhenne, Hubertine Heremans, Jozef Van Damme, Ghislain Opdenakker
RATIONALE: Malaria infection is often complicated by malaria-associated acute respiratory distress syndrome (MA-ARDS), characterized by pulmonary edema and hemorrhages. No efficient treatments are available for MA-ARDS and its pathogenesis remains poorly understood. OBJECTIVES: Development of a new animal model for MA-ARDS to explore the pathogenesis and possible treatments. METHODS: C57BL/6 mice were infected with Plasmodium berghei NK65, and ...

Role of hemozoin in malaria immunopathologies KU Leuven

Katrien Deroost
Malaria is a life-threatening disease caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. According to the annual world malaria report of the World Health Organization, an estimated 216 million people were clinically affected by malaria in 2010 and approximately 655 000 of these patients died from severe complications. Intraerythrocytic parasite replication, cytoadherence to the microvascular endothelium of several organs to ...

von Willebrand factor and ADAMTS13 in mouse models of severe malaria KU Leuven

Sirima Kraisin
Malaria remains a devastating global health problem, leading to half a million deaths per year. More than 90% of malaria cases and deaths occur in African regions, mainly in children aged under 5 years. Cerebral malaria (CM) is the most common complication and cause of death in severe Plasmodium falciparum infection. In addition to CM, malaria-associated acute respiratory distress syndrome (MA-ARDS) is also common in adult patients, leading to a ...