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Updated: Mar 12, 2026

Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
Aspergillus fumigatus CalA binds to integrin α5β1 and mediates host cell invasion
Hong Liu1, Mark J Lee2, Norma V Solis1
1Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Abstract:
Aspergillus fumigatus is an opportunistic fungal pathogen that invades pulmonary epithelial cells and vascular endothelial cells by inducing its own endocytosis, but the mechanism by which this process occurs is poorly understood. Here, we show that the thaumatin-like protein CalA is expressed on the surface of the A. fumigatus cell wall, where it mediates invasion of epithelial and endothelial cells. CalA induces endocytosis in part by interacting with integrin α5β1 on host cells. In corticosteroid-treated mice, a ΔcalA deletion mutant has significantly attenuated virulence relative to the wild-type strain, as manifested by prolonged survival, reduced pulmonary fungal burden and decreased pulmonary invasion. Pretreatment with an anti-CalA antibody improves survival of mice with invasive pulmonary aspergillosis, demonstrating the potential of CalA as an immunotherapeutic target. Thus, A. fumigatus CalA is an invasin that interacts with integrin α5β1 on host cells, induces endocytosis and enhances virulence.
Insights
The fungal pathogen Aspergillus fumigatus uses its surface protein CalA to invade host cells by triggering endocytosis. Targeting CalA shows promise for treating invasive pulmonary aspergillosis.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Aspergillus fumigatus is an opportunistic fungal pathogen.
- It invades pulmonary epithelial and vascular endothelial cells via induced endocytosis.
- The precise mechanism of this invasion is not fully understood.
Purpose of the Study:
- To elucidate the mechanism of Aspergillus fumigatus invasion.
- To identify key fungal factors mediating host cell entry.
- To evaluate CalA as a potential therapeutic target for invasive pulmonary aspergillosis.
Main Methods:
- Investigated the role of the thaumatin-like protein CalA in A. fumigatus invasion.
- Examined CalA's interaction with host cell integrin α5β1.
- Assessed the virulence of a ΔcalA deletion mutant in corticosteroid-treated mice.
- Evaluated the efficacy of anti-CalA antibodies in a murine model of invasive pulmonary aspergillosis.
Main Results:
- CalA is expressed on the A. fumigatus cell surface and mediates invasion of epithelial and endothelial cells.
- CalA interacts with host integrin α5β1, inducing endocytosis.
- A ΔcalA mutant exhibited significantly reduced virulence in mice, with improved survival and lower fungal burden.
- Anti-CalA antibody pretreatment enhanced survival in a murine invasive pulmonary aspergillosis model.
Conclusions:
- A. fumigatus CalA acts as an invasin, interacting with host integrin α5β1 to induce endocytosis and promote fungal virulence.
- CalA is a promising immunotherapeutic target for invasive pulmonary aspergillosis.
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