Stefan Bidula1, Darren W Sexton1, Alireza Abdolrasouli2, Anand Shah2, Anna Reed3, Darius Armstrong-James2, Silke Schelenz4. 1. Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich. 2. Section of Infectious Diseases and Immunity, Imperial College London. 3. Department of Lung Transplantation, Harefield Hospital, Middlesex, United Kingdom. 4. Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Department of Microbiology, Royal Brompton Hospital, London.
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.
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: Kasper Jensen; Kit P Lund; Kimmie B Christensen; Anne T Holm; Lalit Kumar Dubey; Jesper B Moeller; Christine S Jepsen; Anders Schlosser; László Galgóczy; Steffen Thiel; Uffe Holmskov; Grith L Sorensen Journal: Virulence Date: 2017-02-16 Impact factor: 5.882
Authors: A Arastehfar; A Carvalho; J Houbraken; L Lombardi; R Garcia-Rubio; J D Jenks; O Rivero-Menendez; R Aljohani; I D Jacobsen; J Berman; N Osherov; M T Hedayati; M Ilkit; D James-Armstrong; T Gabaldón; J Meletiadis; M Kostrzewa; W Pan; C Lass-Flörl; D S Perlin; M Hoenigl Journal: Stud Mycol Date: 2021-05-10 Impact factor: 16.097
Authors: Stefan Bidula; Darren W Sexton; Matthew Yates; Alireza Abdolrasouli; Anand Shah; Russell Wallis; Anna Reed; Darius Armstrong-James; Silke Schelenz Journal: Immunology Date: 2015-08-24 Impact factor: 7.397
Authors: Nansalmaa Amarsaikhan; Ethan M Sands; Anand Shah; Ali Abdolrasouli; Anna Reed; James E Slaven; Darius Armstrong-James; Steven P Templeton Journal: J Immunol Date: 2017-05-31 Impact factor: 5.422