title: Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.
abstract: 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-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-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 beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/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.
authors.affiliation: Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Hohl
authors.forename: Heather L
authors.initials: HL
authors.lastname: Van Epps
authors.forename: Amariliz
authors.initials: A
authors.lastname: Rivera
authors.forename: Laura A
authors.initials: LA
authors.lastname: Morgan
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Chen
authors.forename: Marta
authors.initials: M
authors.lastname: Feldmesser
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D037181:Lectins, C-Type; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013172:Spores, Fungal / Q000276:immunology*; D047071:beta-Glucans / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047071:beta-Glucans; D000099181:Dectin-1