Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation

Camila Figueiredo Pinzan, Clara Valero, Patrícia Alves de Castro, Jefferson Luiz da Silva, Kayleigh Earle, Hong Liu, Maria Augusta Crivelente Horta, Olaf Kniemeyer, Thomas Krüger, Annica Pschibul, Derya Nur Cömert, Thorsten Heinekamp, Axel A Brakhage, Jacob L Steenwyk, Matthew E Mead, Nico Hermsdorf, Scott G Filler, Nathalia Gonsales da Rosa-Garzon, Endrews Delbaje, Michael J BromleyHamilton Cabral, Camila Diehl, Claudia B Angeli, Giuseppe Palmisano, Ashraf S Ibrahim, David C Rinker, Thomas J C Sauters, Karin Steffen, Adiyantara Gumilang, Antonis Rokas, Sara Gago, Thaila F Dos Reis, Gustavo H Goldman

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Abstract

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.

Original languageEnglish
Pages (from-to)2710-2726
Number of pages17
JournalNature Microbiology
Volume9
Issue number10
Early online date27 Aug 2024
DOIs
Publication statusPublished - 1 Oct 2024

Keywords

  • Animals
  • Aspergillosis/immunology
  • Aspergillus fumigatus/immunology
  • Cytokines/metabolism
  • Disease Models, Animal
  • Epithelial Cells/microbiology
  • Female
  • Fungal Proteins/genetics
  • Host-Pathogen Interactions/immunology
  • Humans
  • Immune Evasion
  • Macrophages/immunology
  • Membrane Proteins/genetics
  • Mice
  • Proteome/genetics
  • Spores, Fungal/immunology

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