title: The serum opsonin L-ficolin is detected in lungs of human transplant recipients following fungal infections and modulates inflammation and killing of Aspergillus fumigatus.
abstract: BACKGROUND
  Invasive aspergillosis (IA) is a life-threatening systemic fungal infection in immunocompromised individuals that is caused by Aspergillus fumigatus. The human serum opsonin, L-ficolin, has been observed to recognize A. fumigatus and could participate in fungal defense.
  
  
  METHODS
  Using lung epithelial cells, primary human monocyte-derived macrophages (MDMs), and neutrophils from healthy donors, we assessed phagocytosis and killing of L-ficolin-opsonized live A. fumigatus conidia by flow cytometry and microscopy. Additionally, cytokines were measured by cytometric bead array, and L-ficolin was measured in bronchoalveolar lavage (BAL) fluid from lung transplant recipients by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  L-ficolin opsonization increased conidial uptake and enhanced killing of A. fumigatus by MDMs and neutrophils. Opsonization was also shown to manifest an increase in interleukin 8 release from A549 lung epithelial cells but decreased interleukin 1β, interleukin 6, interleukin 8, interleukin 10, and tumor necrosis factor α release from MDMs and neutrophils 24 hours after infection. The concentration of L-ficolin in BAL fluid from patients with fungal infection was significantly higher than that for control subjects (P = .00087), and receiving operating characteristic curve analysis highlighted the diagnostic potential of L-ficolin for lung infection (area under the curve, 0.842; P < .0001).
  
  
  CONCLUSIONS
  L-ficolin modulates the immune response to A. fumigatus. Additionally, for the first time, L-ficolin has been demonstrated to be present in human lungs.
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bidula
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich.
authors.forename: Darren W
authors.initials: DW
authors.lastname: Sexton
authors.affiliation: Section of Infectious Diseases and Immunity, Imperial College London.
authors.forename: Alireza
authors.initials: A
authors.lastname: Abdolrasouli
authors.affiliation: Section of Infectious Diseases and Immunity, Imperial College London.
authors.forename: Anand
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Lung Transplantation, Harefield Hospital, Middlesex, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Reed
authors.affiliation: Section of Infectious Diseases and Immunity, Imperial College London.
authors.forename: Darius
authors.initials: D
authors.lastname: Armstrong-James
authors.affiliation: Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Department of Microbiology, Royal Brompton Hospital, London.
authors.forename: Silke
authors.initials: S
authors.lastname: Schelenz
mesh_terms: D001228:Aspergillosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D000097604:Ficolins
chemical_list: D016207:Cytokines; D037102:Lectins; D000097604:Ficolins
keywords: Aspergillus fumigatus; L-ficolin; cytokines; epithelial; lung transplant; macrophage; neutrophil; phagocytosis