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Here we report that lipid-raft microdomains are necessary the different parts of phagolysosomal membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the construction of both major defense complexes vATPase and NADPH oxidase calls for membrane microdomains. Also, we explain a virulence mechanism leading to dysregulation of membrane microdomains by melanized wild-type conidia associated with crucial human-pathogeni