title: A murine inhalation model to characterize pulmonary exposure to dry Aspergillus fumigatus conidia.
abstract: Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Δalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1×105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Δalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants.
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Buskirk
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Green
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Lemons
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Ajay P
authors.initials: AP
authors.lastname: Nayak
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: W Travis
authors.initials: WT
authors.lastname: Goldsmith
authors.affiliation: Biostatistics and Epidemiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Hettick
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Templeton
authors.affiliation: Toxicology Branch, National Toxicology Program Division, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
authors.affiliation: Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, United States of America.
authors.forename: Donald H
authors.initials: DH
authors.lastname: Beezhold
mesh_terms: D000162:Acoustics; D000280:Administration, Inhalation; D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D025301:Hyphae / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008807:Mice, Inbred BALB C; D040901:Proteomics; D013045:Species Specificity; D013172:Spores, Fungal / Q000502:physiology*
chemical_list: D000908:Antibodies, Fungal; D016207:Cytokines; D007074:Immunoglobulin G