Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins.

Details

Serval ID
serval:BIB_67399C7CCE1D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins.
Journal
The Journal of biological chemistry
Author(s)
Shende R., Wong SSW, Rapole S., Beau R., Ibrahim-Granet O., Monod M., Gührs K.H., Pal J.K., Latgé J.P., Madan T., Aimanianda V., Sahu A.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Publication state
Published
Issued date
05/10/2018
Peer-reviewed
Oui
Volume
293
Number
40
Pages
15538-15555
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Innate immunity in animals including humans encompasses the complement system, which is considered an important host defense mechanism against Aspergillus fumigatus, one of the most ubiquitous opportunistic human fungal pathogens. Previously, it has been shown that the alkaline protease Alp1p secreted from A. fumigatus mycelia degrades the complement components C3, C4, and C5. However, it remains unclear how the fungal spores (i.e. conidia) defend themselves against the activities of the complement system immediately after inhalation into the lung. Here, we show that A. fumigatus conidia contain a metalloprotease Mep1p, which is released upon conidial contact with collagen and inactivates all three complement pathways. In particular, Mep1p efficiently inactivated the major complement components C3, C4, and C5 and their activation products (C3a, C4a, and C5a) as well as the pattern-recognition molecules MBL and ficolin-1, either by directly cleaving them or by cleaving them to a form that is further broken down by other proteases of the complement system. Moreover, incubation of Mep1p with human serum significantly inhibited the complement hemolytic activity and conidial opsonization by C3b and their subsequent phagocytosis by macrophages. Together, these results indicate that Mep1p associated with and released from A. fumigatus conidia likely facilitates early immune evasion by disarming the complement defense in the human host.
Keywords
Animals, Aspergillus fumigatus/growth & development, Aspergillus fumigatus/immunology, Aspergillus fumigatus/pathogenicity, Collagen/genetics, Collagen/immunology, Complement C3/genetics, Complement C3/metabolism, Complement C4/genetics, Complement C4/metabolism, Complement C5/genetics, Complement C5/metabolism, Disease Models, Animal, Fungal Proteins/genetics, Fungal Proteins/immunology, Gene Expression Regulation, Host-Pathogen Interactions, Humans, Immune Evasion, Immunity, Innate, Invasive Pulmonary Aspergillosis/genetics, Invasive Pulmonary Aspergillosis/immunology, Invasive Pulmonary Aspergillosis/microbiology, Invasive Pulmonary Aspergillosis/pathology, Lectins/genetics, Lectins/immunology, Lung/immunology, Lung/pathology, Macrophages/immunology, Macrophages/microbiology, Male, Mannose-Binding Protein-Associated Serine Proteases/genetics, Mannose-Binding Protein-Associated Serine Proteases/immunology, Metalloendopeptidases/deficiency, Metalloendopeptidases/genetics, Metalloendopeptidases/immunology, Mice, Mice, Inbred BALB C, Mice, Knockout, Phagocytosis, Spores, Fungal/growth & development, Spores, Fungal/immunology, Spores, Fungal/pathogenicity, Aspergillus, Aspergillus fumigatus, complement, complement system, immune evasion, infectious disease, inflammation, metalloprotease, phagocytosis
Pubmed
Web of science
Create date
17/10/2018 9:42
Last modification date
16/02/2021 6:27
Usage data