1. Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins
- Author
-
Michel Monod, Oumaïma Ibrahim-Granet, Rajashri Shende, Rémi Beau, Jean-Paul Latgé, Karl-Heinz Gührs, Taruna Madan, Jayanta K. Pal, Arvind Sahu, Vishukumar Aimanianda, Sarah Sze Wah Wong, Srikanth Rapole, Savitribai Phule Pune University [Pune, india], Aspergillus, Institut Pasteur [Paris], Cytokines et Inflammation, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, National Institute for Research in Reproductive Health [Mumbai, India] (ICMR), This work was supported in part by a bilateral COMASPIN grant from the Department of Science and Technology (DST) India and l'Agence Nationale de la Recherché (ANR) France, and Institut Pasteur [Paris] (IP)
- Subjects
0301 basic medicine ,metalloprotease ,[SDV]Life Sciences [q-bio] ,Host Defense Mechanism ,Biochemistry ,MESH: Mice, Knockout ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Aspergillus fumigatus ,MESH: Lectins ,MESH: Collagen ,complement ,MESH: Animals ,MESH: Immune Evasion ,MESH: Phagocytosis ,biology ,Chemistry ,phagocytosis ,MESH: Complement C3 ,MESH: Complement C4 ,MESH: Gene Expression Regulation ,Antibody opsonization ,Aspergillus ,MESH: Complement C5 ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Immunity, Innate ,MESH: Fungal Proteins ,MESH: Aspergillus fumigatus ,Proteases ,MESH: Invasive Pulmonary Aspergillosis ,infectious disease ,Immunology ,MESH: Mice, Inbred BALB C ,MESH: Metalloendopeptidases ,Microbiology ,03 medical and health sciences ,Immune system ,MESH: Spores, Fungal ,MESH: Lung ,Molecular Biology ,MESH: Mice ,complement system ,immune evasion ,Innate immune system ,MESH: Humans ,MESH: Host-Pathogen Interactions ,C4A ,MESH: Macrophages ,Cell Biology ,biology.organism_classification ,MESH: Male ,Complement system ,030104 developmental biology ,MESH: Mannose-Binding Protein-Associated Serine Proteases ,inflammation ,MESH: Disease Models, Animal - Abstract
International audience; 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.
- Published
- 2018
- Full Text
- View/download PDF