title: The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum.
abstract: Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus onExserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosingExserohilumDespite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production.In vivosoft tissue infection in wild-type mice demonstrated thatExserohilumprovokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response toExserohilumand that corticosteroids potently attenuate the immune response to this pathogen.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reedy
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Paige E
authors.initials: PE
authors.lastname: Negoro
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Marianela
authors.initials: M
authors.lastname: Feliu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Lord
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Nida S
authors.initials: NS
authors.lastname: Khan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Dan P
authors.initials: DP
authors.lastname: Lukason
authors.affiliation: The University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Wiederhold
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Tam
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Mansour
authors.affiliation: The University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA jvyas@mgh.harvard.edu.|Harvard Medical School, Department of Medicine, Boston, Massachusetts, USA.
authors.forename: Jatin M
authors.identifier: http://orcid.org/0000-0002-9985-9565
authors.initials: JM
authors.lastname: Vyas
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001203:Ascomycota / Q000187:drug effects / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D025301:Hyphae; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009181:Mycoses / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis; D013172:Spores, Fungal; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D002241:Carbohydrates; D016207:Cytokines; D037181:Lectins, C-Type; D014409:Tumor Necrosis Factor-alpha; D000099181:Dectin-1
keywords: Dectin-1; Exserohilum; fungi; macrophages; molds