Functional surface proteomic profiling reveals the host heat-shock proteinA8as a mediator ofLichtheimia corymbiferarecognition by murine alveolar macrophages
Open Access
- 1 September 2020
- journal article
- research article
- Published by Wiley in Environmental Microbiology
- Vol. 22 (9), 3722-3740
- https://doi.org/10.1111/1462-2920.15140
Abstract
Mucormycosis is an emergent, fatal fungal infection of humans and warm-blooded animals caused by species of the order Mucorales. Immune cells of the innate immune system serve as the first line of defence against inhaled spores. Alveolar macrophages were challenged with the mucoralean fungusLichtheimia corymbiferaand subjected to biotinylation and streptavidin enrichment procedures followed by LC-MS/MS analyses. A total of 28 host proteins enriched for binding to macrophage-L.corymbiferainteraction. Among those, the HSP70-family protein Hspa8 was found to be predominantly responsive to living and heat-killed spores of a virulent and an attenuated strain ofL.corymbifera. Confocal scanning laser microscopy of infected macrophages revealed colocalization of Hspa8 with phagocytosed spores ofL.corymbifera. The amount of detectable Hspa8 was dependent on the multiplicity of infection. Incubation of alveolar macrophages with an anti-Hspa8 antibody prior to infection reduced their capability to phagocytose spores ofL.corymbifera. In contrast, anti-Hspa8 antibodies did not abrogate the phagocytosis ofAspergillus fumigatusconidia by macrophages. These results suggest an important contribution of the heat-shock family protein Hspa8 in the recognition of spores of the mucoralean fungusL.corymbiferaby host alveolar macrophages and define a potential immunomodulatory therapeutic target.Funding Information
- Bundesministerium für Bildung und Forschung (01ZX1302B, 01ZX1602B)
- Center for Sepsis Control and Care (01EO1002, 01EO1502)
- Deutsche Forschungsgemeinschaft (SFB/TR 124, A6, A1, A5, B4, Z2)
- Deutscher Akademischer Austausch Dienst Kairo (German Egyptian Research Long‐term Scholarship)
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