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Microglial immune response is impaired against the neurotropic fungus Lomentospora prolificans
Aize Pellon1,2, Andoni Ramirez-Garcia1, Xabier Guruceaga1
1Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain.
Abstract:
Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of causing invasive infections in immunocompromised patients. The fungus is able to disseminate via the bloodstream finally arriving at the central nervous system producing neurological symptoms and, in many cases, patient death. In this context, microglial cells, which are the resident immune cells in the central nervous system, may play an important role in these infections. However, this aspect of anti-L. prolificans immunity has been poorly researched to date. Thus, the interactions and activity of microglial cells against L. prolificans were analysed, and the results show that there was a remarkable impairment in their performance regarding phagocytosis, the development of oxidative burst, and in the production of pro-inflammatory cytokines, compared with macrophages. Interestingly, L. prolificans displays great growth also when challenged with immune cells, even when inside them. We also proved that microglial phagocytosis of the fungus is highly dependent on mannose receptor and especially on dectin-1. Taken together, these data provide evidence for an impaired microglial response against L. prolificans and contribute to understanding the pathobiology of its neurotropism.
Insights
Microglial cells show impaired responses against the opportunistic fungus Lomentospora prolificans, hindering the immune system
Area of Science:
- Mycology
- Immunology
- Neuroscience
Background:
- Lomentospora prolificans is an opportunistic pathogen causing invasive infections, particularly in immunocompromised individuals.
- Dissemination to the central nervous system can lead to severe neurological symptoms and mortality.
- The role of microglial cells in anti-L. prolificans immunity is poorly understood.
Purpose of the Study:
- To analyze the interactions and activity of microglial cells against L. prolificans.
- To investigate the mechanisms underlying microglial phagocytosis of L. prolificans.
Main Methods:
- Comparative analysis of microglial cell performance (phagocytosis, oxidative burst, cytokine production) against L. prolificans versus macrophages.
- Assessment of L. prolificans growth when challenged with immune cells.
- Investigation of the role of mannose receptor and dectin-1 in microglial phagocytosis.
Main Results:
- Microglial cells exhibited impaired phagocytosis, oxidative burst, and pro-inflammatory cytokine production compared to macrophages.
- L. prolificans demonstrated significant growth even when internalizing immune cells.
- Microglial phagocytosis of L. prolificans was significantly dependent on mannose receptor and dectin-1.
Conclusions:
- Microglial cells display an impaired immune response against L. prolificans.
- These findings contribute to understanding the neurotropism of L. prolificans and its pathogenesis in the central nervous system.
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