Journal Article

Aspergillus fumigatus effector crpA orchestrates host prostaglandin signaling to promote fungal virulence

Rocha, Peter, da Rosa-Garzon, Nathalia Gonsales, de Castro, Patrícia Alves, Cunha, Larissa Dias, Sorgi, Carlos Arterio, Rosowski, Emily E., Ecoutin, Agathe, Marciano, Camila Langer, Vilela, Adriana Ferreira Lopes, Loquet, Antoine, Diehl, Camila, dos Reis, Thaila Fernanda, Sprute, Rosanne, Kolovou, Androniki, Berbon, Mélanie, Delbaje, Endrews, Goldman, Gustavo H., Thrikawala, Savini U., Pinzan, Camila Figueiredo, Cabral, Hamilton, Freitas-Filho, Edismauro Garcia

2025

Overview

Conidia serve as the primary infectious units of Aspergillus fumigatus , the causative agent of aspergillosis. This study identifies CrpA, a cysteine-rich protein found on the conidial surface, as a crucial regulator of immune modulation and fungal virulence. Loss of CrpA (Δ crpA ) alters host immune responses, resulting in reduced production of proinflammatory cytokines and increased IL-10 levels in both murine macrophages and infected lungs. ΔcrpA conidia also stimulate elevated levels of prostaglandins PGE2 and PGD2. This immunomodulatory effect is dependent on eicosanoid signaling as the virulence of Δ crpA is restored in prostaglandin-deficient zebrafish larvae. CrpA directly modulates macrophage production of PGE2 and cytokines. Solid-state NMR analysis shows that Δ crpA conidia expose lower levels of β−1,3-glucan and chitin, suggesting that CrpA influences both cell wall composition and host pattern recognition receptor engagement. Δ crpA strains are avirulent in immunocompetent mice, and patients with invasive pulmonary aspergillosis exhibit elevated CrpA-specific IgG. These results highlight CrpA as a key virulence factor in A. fumigatus and a promising target for antifungal therapy.

• Publisher: American Society for Microbiology
• Subject: Amino acids / Animal models / Animals / Antisera / Aspergillosis / Aspergillosis - immunology / Aspergillosis - microbiology / Aspergillus fumigatus / Aspergillus fumigatus - genetics / Aspergillus fumigatus - immunology / Aspergillus fumigatus - metabolism / Aspergillus fumigatus - pathogenicity / Aspergillus Pathogenesis / Biological products / Cell walls / Chemical Sciences / Chitin / Clinical Microbiology and Infectious Diseases / Conidia / Cysteine / Cytokines / Cytokines - metabolism / Danio rerio / Dehydrogenases / Disease / Disease Models, Animal / Epidermal growth factor / Female / Fungal Immune Evasion / Fungal Immunity / Fungal Infections / Fungal Pathogenesis / Fungal Proteins - genetics / Fungal Proteins - metabolism / Fungal Virulence Factors / Genes / Host-Fungal Interactions / Host-Microbial Interactions / Host-Pathogen Interactions / Immune response / Immunity (Disease) / Immunocompetence / Immunoglobulin G / Immunomodulation / Inflammation / Interleukin 10 / Life Sciences / Macrophages / Macrophages - immunology / Macrophages - microbiology / Mice / Microbial Pathogenesis and Immunology / Mutants / NMR / Nuclear magnetic resonance / Pathogen-Specific Immunity / Pathogenesis / Pathogens / Pattern recognition receptors / Phylogenetics / prostaglandin / Prostaglandin E2 / Prostaglandins - metabolism / Proteins / Research Article / Signal Transduction / solid-state NMR / Spores, Fungal - genetics / Spores, Fungal - pathogenicity / Statistical analysis / Viral infections / Virulence / Virulence factors / Virulence Factors - genetics / Virulence Factors - metabolism / Waste Management and Infection Risk / Zebrafish