MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus
Year: 2022
Type: article
Abstract: ABSTRACT Our recent data demonstrates a critical role of the RIG-I-like receptor (RLR) family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell type(s) which utilize this innate immune receptor to detect A. fumigatus remains unresolved. Here using patients who underwent hematopoietic stem cell transplantation (HSCT), we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis (IPA). Moreover, in a separate cohort of confirmed IPA patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including interferon-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c + SiglecF + 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 human at least in part through the role of MAVS-dependent signaling in alveolar macrophages.
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Dartmouth College, European Commission, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, Audrey and Theodor Geisel School of Medicine at Dartmouth, Fundação para a Ciência e a Tecnologia, European Regional Development Fund, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, NHLBI Division of Intramural Research
Awards: G1255325603, G1516346500, G1621359206, A interação hospedeiro-microbiota: novos biomarcadores e terapia na infeção fúngica invasiva, G229447181, Host directed medicine in invasive fungal infection, ICVS/3B’s - Laboratório Associado, Instituto de Ciências da Vida e da Saúde / Grupo de Investigação em Biomateriais, Biodegradaveis e Biomiméticos, G3493467044, G3525276842, G3660205263, ICVS/3B’s - Laboratório Associado, Instituto de Ciências da Vida e da Saúde / Grupo de Investigação em Biomateriais, Biodegradaveis e Biomiméticos, Center for Molecular, Cellular, and Translational Immunology, G4316116677, G434337789, G450822820, G477297383, G5132640529, G5454278309, G5726560303, G5955501538, G6004110409, G694974824, HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases, G7584003722, G7661467656, G7685134749, G7731791180, G9000010379, G9000099017, Fungal spore sensing by MDA5 is necessary for antifungal immunity against Aspergillus fumigatus, G96847669
OpenAlex ID: W4283523879