MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus
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Updated: Sep 6, 2025
Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
Xi Wang1, Cristina Cunha2,3, Madeleine S Grau1
1Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
Abstract:
Our recent data demonstrate a critical role of the RIG-I-like receptor family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell types that use this innate immune receptor family to detect A. fumigatus remain unresolved. In this study, using patients who underwent hematopoietic stem cell transplantation, we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis. Moreover, in a separate cohort of confirmed invasive pulmonary aspergillosis patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including IFN-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c+ Siglec F+ alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and humans at least in part through the role of MAVS-dependent signaling in alveolar macrophages.
Insights
RIG-I-like receptor signaling, specifically MAVS, is crucial for antifungal immunity against Aspergillus fumigatus. This pathway in alveolar macrophages protects against invasive pulmonary aspergillosis in both mice and humans.
Area of Science:
- Immunology
- Infectious Diseases
- Genetics
Background:
- The RIG-I-like receptor (RLR) family is vital for innate immunity against fungal pathogens like Aspergillus fumigatus.
- The specific role of RLRs in human antifungal immunity and the involved cell types remain unclear.
Purpose of the Study:
- To investigate the role of MAVS signaling in human and murine antifungal immunity against Aspergillus fumigatus.
- To identify the specific immune cells utilizing MAVS for Aspergillus fumigatus detection.
Main Methods:
- Analysis of MAVS and IFIH1 gene polymorphisms in hematopoietic stem cell transplant patients and invasive pulmonary aspergillosis patients.
- Murine models were used to assess the function of MAVS in alveolar macrophages during Aspergillus fumigatus infection.
Main Results:
- A polymorphism in the donor MAVS gene was linked to invasive pulmonary aspergillosis incidence.
- IFIH1 gene polymorphisms affected inflammatory responses, including IFN-responsive chemokines, in aspergillosis patients.
- Mavs expression in CD11c+ Siglec F+ alveolar macrophages is essential for host resistance against Aspergillus fumigatus in mice.
Conclusions:
- MAVS signaling plays a critical role in mediating antifungal immunity against Aspergillus fumigatus in both mice and humans.
- MAVS-dependent signaling in alveolar macrophages is a key mechanism for host defense against invasive pulmonary aspergillosis.
