The intraphagocytic long-term survival of the mucormycotic agent Lichtheimia corymbifera
Lichtheimia corymbifera is one of the causative agents for mucormycosis with a high mortality up to 90 % in humans. It mainly affects immunocompromised as well as poorly controlled diabetic patients. The airborne spores of the fungus can enter the lungs via inhalation. Once the spores reach the lungs, they encounter the first line of defence of the innate immunity such as alveolar macrophages. Currently, little is known about the interplay between L. corymbifera and alveolar macrophages. The study of the interaction between the fungus and the host cells will improve our understanding of the infection process. This thesis work shows that L. corymbifera can be recognised and phagocytosed by macrophages. Subsequently, the spores persist as a spore stage inside the macrophages without hyphal formation and damage to the host cells. Internalised spores interfere with the phagosome maturation by inhibiting the fusion of phagosome and lysosome, which allows a long-term survival of L. corymbifera within the macrophages. It was also found that the inhibition of phagosome maturation is dependent on the viability of the spores as well as surface factor(s), indicating a metabolically active interference of the fungus for the persistence inside the host cells. This persistence then may enable the fungus to evade the immune cells and even utilise the infected cells like macrophages to systemically disseminate within the host. In addition, investigation of two different L. corymbifera isolates revealed differences in their recognition by components of the complement system. Furthermore, surface proteomic analysis showed differences in the abundances of some proteins (e.g., HsbA) which may result in the differences in the recognition by the alveolar macrophage. Overall, the data represent valuable asset for the future research in revealing the underlying mechanisms of host pathogen interaction which may serve to develop new therapeutic approaches to fight mucormycosis.
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