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Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosome...

Jia, Lei-Jie; Rafiq, Muhammad; Radosa, Lukáš; Hortschansky, Peter; Cunha, Cristina; Cseresnyés, Zoltán; Krüger, Thomas; Schmidt, Franziska

The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes ...


Phagosomal removal of fungal melanin reprograms macrophage metabolism to promot...

Gonçalves, Samuel M.; Duarte-Oliveira, Cláudio; Campos, Cláudia F.; Aimanianda, Vishukumar; ter Horst, Rob; Leite, Luis; Mercier, Toine

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestrat...


Flotillin-dependent membrane microdomains are required for functional phagolyso...

Schmidt, Franziska; Thywißen, Andreas; Goldmann, Marie; Cunha, Cristina; Cseresnyés, Zoltán; Schmidt, Hella; Rafiq, Muhammad; Galiani, Silvia

Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdo...


Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling ...

Kyrmizi, Irene; Ferreira, Helena; Carvalho, Agostinho; Figueroa, Julio Alberto Landero; Zarmpas, Pavlos; Cunha, Cristina; Akoumianaki, Tonia

LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulati...


Recognition of DHN-melanin by a C-type lectin receptor is required for immunity...

Stappers, Mark H.T.; Clark, Alexandra E.; Aimanianda, Vishukumar; Bidula, Stefan; Reid, Delyth M.; Asamaphan, Patawee; Hardison, Sarah E.

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically a...


Recognition of DHN-melanin by a C-type lectin receptor is required for immunity...

Stappers, Mark H. T.; Clark, Alexandra E.; Aimanianda, Vishukumar; Bidula, Stefan; Reid, Delyth M.; Asamaphan, Patawee; Hardison, Sarah E.

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically a...


Calcium sequestration by fungal melanin inhibits calcium–calmodulin signalling ...

Kyrmizi, Irene; Ferreira, Helena; Carvalho, Agostinho; Figueroa, Julio Alberto Landero; Zarmpas, Pavlos; Cunha, Cristina; Akoumianaki, Tonia

LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulati...


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