TY - JOUR
T1 - Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation
AU - Pinzan, Camila Figueiredo
AU - Valero, Clara
AU - de Castro, Patrícia Alves
AU - da Silva, Jefferson Luiz
AU - Earle, Kayleigh
AU - Liu, Hong
AU - Horta, Maria Augusta Crivelente
AU - Kniemeyer, Olaf
AU - Krüger, Thomas
AU - Pschibul, Annica
AU - Cömert, Derya Nur
AU - Heinekamp, Thorsten
AU - Brakhage, Axel A
AU - Steenwyk, Jacob L
AU - Mead, Matthew E
AU - Hermsdorf, Nico
AU - Filler, Scott G
AU - da Rosa-Garzon, Nathalia Gonsales
AU - Delbaje, Endrews
AU - Bromley, Michael J
AU - Cabral, Hamilton
AU - Diehl, Camila
AU - Angeli, Claudia B
AU - Palmisano, Giuseppe
AU - Ibrahim, Ashraf S
AU - Rinker, David C
AU - Sauters, Thomas J C
AU - Steffen, Karin
AU - Gumilang, Adiyantara
AU - Rokas, Antonis
AU - Gago, Sara
AU - Dos Reis, Thaila F
AU - Goldman, Gustavo H
N1 - © 2024. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.
AB - Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.
KW - Animals
KW - Aspergillosis/immunology
KW - Aspergillus fumigatus/immunology
KW - Cytokines/metabolism
KW - Disease Models, Animal
KW - Epithelial Cells/microbiology
KW - Female
KW - Fungal Proteins/genetics
KW - Host-Pathogen Interactions/immunology
KW - Humans
KW - Immune Evasion
KW - Macrophages/immunology
KW - Membrane Proteins/genetics
KW - Mice
KW - Proteome/genetics
KW - Spores, Fungal/immunology
UR - http://www.scopus.com/inward/record.url?scp=85202208708&partnerID=8YFLogxK
U2 - 10.1038/s41564-024-01782-y
DO - 10.1038/s41564-024-01782-y
M3 - Article
C2 - 39191887
SN - 2058-5276
VL - 9
SP - 2710
EP - 2726
JO - Nature Microbiology
JF - Nature Microbiology
IS - 10
ER -