Aspergillus fumigatus conidial metalloprotease Mep1p cleaves host complement proteins
| Autor: | 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 |
|---|---|
| Přispěvatelé: | 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, Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2018, 293 (40), pp.15538-15555. ⟨10.1074/jbc.RA117.001476⟩ Journal of Biological Chemistry, 2018, 293 (40), pp.15538-15555. ⟨10.1074/jbc.RA117.001476⟩ |
| ISSN: | 0021-9258 1083-351X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|