CARD9 deficiency predisposing chromoblastomycosis: A case report and comparative transcriptome study.

Area of Science:

• Medical Mycology
• Immunogenetics

Background:

• Card9 (Caspase Recruitment Domain-Containing Protein 9) mutations are linked to susceptibility to phaeohyphomycosis, a fungal infection caused by dematiaceous fungi.
• Chromoblastomycosis is a distinct form of subcutaneous mycosis caused by dematiaceous fungi.

Observation:

• This study reports the first case of chromoblastomycosis caused by Phialophora expanda in a patient with a CARD9 mutation.
• Comparative in vivo and in vitro studies were conducted, including transcriptome analysis, comparing this case with a previous patient with phaeohyphomycosis caused by Phialophora americana.

Findings:

• Phialophora expanda demonstrates a propensity for forming sclerotic bodies in vitro and in Card9 knockout mice.
• Phialophora expanda exhibits stronger immunogenicity compared to Phialophora americana.
• Fungal species-specific characteristics contribute to the clinical manifestations in CARD9-deficient patients with dematiaceous fungal infections.

Implications:

• Understanding fungal specificity is crucial for predicting disease outcomes in CARD9-deficient individuals.
• This research highlights the interplay between host genetic factors (CARD9 mutations) and fungal pathogen traits in determining the clinical phenotype of mycoses.
• Further research into fungal immunogenicity can inform therapeutic strategies for invasive fungal infections in immunocompromised patients.