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Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype

Bhatia, S and Fei, M and Yarlagadda, M and Qi, Z and Akira, S and Saijo, S and Iwakura, Y and van Rooijen, N and Gibson, GA and St. Croix, CM and Ray, A and Ray, P (2011) Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype. PLoS ONE, 6 (1).

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Abstract

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. © 2011 Bhatia et al. +


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bhatia, S
Fei, M
Yarlagadda, M
Qi, ZZEQ7@pitt.eduZEQ7
Akira, S
Saijo, S
Iwakura, Y
van Rooijen, N
Gibson, GAgregory.gibson@pitt.eduGAGST18
St. Croix, CM
Ray, Araya@pitt.eduRAYA
Ray, Prayp@pitt.eduRAYP
Date: 1 February 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0015943
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
School of Medicine > Immunology
Refereed: Yes
MeSH Headings: Animals; Arginase--immunology; Aspergillus fumigatus--immunology; Cells, Cultured; Gene Expression; Immunity; Macrophages, Alveolar--immunology; Macrophages, Alveolar--metabolism; Macrophages, Alveolar--microbiology; Membrane Proteins--immunology; Mice; Nerve Tissue Proteins--immunology; Opportunistic Infections; Phagocytosis--immunology; Phenotype
Other ID: NLM PMC3016416
PubMed Central ID: PMC3016416
PubMed ID: 21246055
Date Deposited: 03 Aug 2012 18:44
Last Modified: 30 Mar 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/13251

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