Protective role of host complement system in Aspergillus fumigatus infection
| Autor: | Rajashri Shende, Sarah Sze Wah Wong, Heikrujam Thoihen Meitei, Girdhari Lal, Taruna Madan, Vishukumar Aimanianda, Jayanta Kumar Pal, Arvind Sahu |
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| Přispěvatelé: | Savitribai Phule Pune University [India], Dr. D. Y. Patil Vidyapeeth [Pune] (DPU), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Département de Mycologie - Department of Mycology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), National Institute for Research in Reproductive and Child Health [Mumbai] (NIRRCH), AS is a J.C. Bose National Fellow. His lab is supported by the Department of Biotechnology, India, Project Grant BT/PR28506/MED/29/1307/2018. VA was supported by FUNHYDRO (ANR-16S-CE110020-01) and FUNPOLYVAC (ANR-21-CE17-0032) grants. SW was supported by Pasteur-Roux-Cantarini postdoctoral fellowship., ANR-16-CE11-0020,FUNHYDRO,Amyloïdes fonctionnels formés par les hydrophobines du pathogène fongique Aspergillus fumigatus(2016), ANR-21-CE17-0032,FUNPOLYVAC,Explorer les polysaccharides fongiques de la paroi cellulaire pour les immunothérapies(2021) |
| Rok vydání: | 2022 |
| Předmět: |
Aspergillus fumigatus
infectious disease Immunology MESH: Complement Factor B MESH: Spores Fungal MESH: Complement C5 [SDV.IMM]Life Sciences [q-bio]/Immunology Immunology and Allergy MESH: Animals MESH: Lung MESH: Aspergillosis MESH: Aspergillus fumigatus innate immunity MESH: Mice complement system [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology systemic aspergillosis |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, 2022, 13, pp.978152. ⟨10.3389/fimmu.2022.978152⟩ |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2022.978152 |
| Popis: | Invasive aspergillosis (IA) is a life-threatening fungal infection for immunocompromised hosts. It is, therefore, necessary to understand the immune pathways that control this infection. Although the primary infection site is the lungs, aspergillosis can disseminate to other organs through unknown mechanisms. Herein we have examined thein vivorole of various complement pathways as well as the complement receptors C3aR and C5aR1 during experimental systemic infection byAspergillus fumigatus, the main species responsible for IA. We show that C3 knockout (C3-/-) mice are highly susceptible to systemic infection ofA. fumigatus. Intriguingly, C4-/-and factor B (FB)-/-mice showed susceptibility similar to the wild-type mice, suggesting that either the complement pathways display functional redundancy during infection (i.e., one pathway compensates for the loss of the other), or complement is activated non-canonically byA. fumigatusprotease. Ourin vitrostudy substantiates the presence of C3 and C5 cleaving proteases inA. fumigatus. Examination of the importance of the terminal complement pathway employing C5-/-and C5aR1-/-mice reveals that it plays a vital role in the conidial clearance. This, in part, is due to the increased conidial uptake by phagocytes. Together, our data suggest that the complement deficiency enhances the susceptibility to systemic infection byA. fumigatus. |
| Databáze: | OpenAIRE |
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