Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan Display

PLoS Pathogens

Marta Feldmesser¹  Eric G Pamer¹  Laura A Morgan²  Amariliz Rivera²  Patrick L Chen²  Heather L. Van Epps²  Tobias M Hohl³ 

[1] Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York, United States of America;Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America;Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

关键词: Aspergillus fumigatus;    Immune response;    Inflammation;    Enzyme-linked immunoassays;    Immune receptor signaling;    Macrophages;    Fungal spore germination;    Fungal spores;   

DOI  :  10.1371/journal.ppat.0010030

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-α/MIP-2 secretion by alveolar macrophages. Fungal β-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal β-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed β-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-α/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.

【 授权许可】

CC BY