The Serum Opsonin L-ficolin Is Detected in Lungs of Human Transplant Recipients Following Fungal Infections and Modulates Inflammation and Killing of Aspergillus fumigatus

Stefan Bidula, Darren W. Sexton, Alireza Abdolrasouli, Anand Shah, Anna Reed, Darius Armstrong-James, Silke Schelenz

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)234-246
Number of pages13
JournalThe journal of infectious diseases
Volume212
Issue number2
Early online date22 Jan 2015
DOIs
Publication statusPublished - 15 Jul 2015

Keywords

  • L-ficolin
  • Aspergillus fumigatus
  • macrophage
  • neutrophil
  • epithelial
  • phagocytosis
  • cytokines
  • lung transplant

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