Rapid Host Defense against Aspergillus fumigatus Involves Alveolar Macrophages with a Predominance of Alternatively Activated Phenotype

PLoS One

Nico van Rooijen¹  Claudette M. St. Croix¹  Yoichiro Iwakura²  Gregory A. Gibson²  Prabir Ray³  Manohar Yarlagadda⁴  Anuradha Ray⁵  Shikha Bhatia⁶  Shizuo Akira⁶  Zengbiao Qi⁶  Mingjian Fei⁶  Shinobu Saijo⁷ 

[1] CREST, Japan Science and Technology Agency, Saitama, Japan;Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America;Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America;Department of Molecular Cell Biology, Vrije Universiteit, Vanderbilt University Medical Center, Amsterdam, The Netherlands;Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America;Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka, Japan

关键词: Alveolar macrophages;    Fungal diseases;    Aspergillus fumigatus;    Macrophages;    Gene expression;    Phagocytosis;    Fungi;    Aspergillus;   

DOI  :  10.1371/journal.pone.0015943

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1), a key marker of alternatively activated macrophages (AAMs). The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.

【 授权许可】

CC BY