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The heat shock protein family A (HSPA8) acts as a surface receptor of alveolar macrophages specific for recognition and phagocytosis of Lichtheimia corymbifera spores

ABSTRACT: Mucormycosis is a life-threatening disease especially in immunocompromised patients that was caused my mucoralean fungi. The rate of mortality is tremendously increased in the last decades due to the lack of appropriate diagnostic tools, insufficient knowledge about the immune response toward the mucormycosis and unavailability of specific antifungal drugs. Several species of mucoralean fungi cause mucormycosis such as Lichtheimia, Rhizopus, and Mucor. Lichtheimia species ranks the second and third cause of mucormycosis in Europe and the USA, respectively. In this study, we investigated the receptors present on the surface of immune cells that bind to the spores of Lichtheimia. We focus on two strains of L. corymbifera (FSU:9682 and FSU:10164) using resting and heat-killed spores. Additionally, we choose alveolar macrophages (MH-S) to carry out our experiment. MH-S is the first line of defense in the lung and the major component in the innate immune system. MH-S surface proteins were biotinylated and incubated with Lichtheimia spores. The surface proteins and putative binding partners were enriched by streptavidin. LC-MS/MS analysis showed that several proteins are highly expressed in presence of Lichtheimia spores, of which the heat shock protein family A (HSPA8) was one of the most abundant proteins. FACS analysis and immunofluorescence examination confirmed that HSPA8 is highly abundant on the surface of the MH-S, but not on the surface of Lichtheimia spores. Moreover, our study showed that the intensity of HSPA8 on the surface of MH-S depends on the multiplicity of infection (MOI). Additionally, the blocking with anti-HSPA8 antibody reduced the capability of MH-S to engulf the Lichtheimia spores, but not Aspergillus fumigatus spores. This confirms that HSPA8 is specific to Lichtheimia. THis is the first study addressing the determination of surface receptors of alveolar macrophages that in the context of Mucoralean fungi.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Lichtheimia Corymbifera Jmrc:fsu:9682 Mus Musculus (mouse)

TISSUE(S): Macrophage

SUBMITTER: Thomas Krüger

LAB HEAD: Axel A. Brakhage

PROVIDER: PXD014197 | Pride | 2020-07-17

REPOSITORIES: Pride

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Functional surface proteomic profiling reveals the host heat-shock protein A8 as a mediator of Lichtheimia corymbifera recognition by murine alveolar macrophages.

Hassan Mohamed I Abdelwahab MIA Kruse Janis M JM Krüger Thomas T Dahse Hans-Martin HM Cseresnyés Zoltán Z Blango Matthew G MG Slevogt Hortense H Hörhold Franziska F Ast Volker V König Rainer R Figge Marc Thilo MT Kniemeyer Olaf O Brakhage Axel A AA Voigt Kerstin K

Environmental microbiology 20200721 9

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 fungus Lichtheimia corymbifera and 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. corymbifera inte ...[more]

PMID: 32583550

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			Action	DRS
	10164-I-SV-a.msf	Msf
	10164-I-SV-a.raw	Raw
	10164-I-SV-b.msf	Msf
	10164-I-SV-b.raw	Raw
	10164-I-SV.fasta	Fasta