Journal of Fungi (Jul 2024)

Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis

  • Marilena Pariano,
  • Anna Gidari,
  • Claudia Stincardini,
  • Sara Pierucci,
  • Sabrina Bastianelli,
  • Matteo Puccetti,
  • Stefano Giovagnoli,
  • Marina M. Bellet,
  • Consuelo Fabi,
  • Roberto Castronari,
  • Cinzia Antognelli,
  • Claudio Costantini,
  • Maurizio Ricci,
  • Daniela Francisci,
  • Luigina Romani

DOI
https://doi.org/10.3390/jof10070510
Journal volume & issue
Vol. 10, no. 7
p. 510

Abstract

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Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.

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