The serum opsonin L-ficolin is detected in lungs of human transplant recipients following fungal infections and modulates inflammation and killing of Aspergillus fumigatus.
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.
['Bidula|Stefan|S|', 'Sexton|Darren W|DW|', 'Abdolrasouli|Alireza|A|', 'Shah|Anand|A|', 'Reed|Anna|A|', 'Armstrong-James|Darius|D|', 'Schelenz|Silke|S|']
D001228:Aspergillosis D001232:Aspergillus fumigatus D045744:Cell Line, Tumor D016207:Cytokines D006801:Humans D007113:Immunity, Innate D037102:Lectins D008168:Lung D016040:Lung Transplantation D008264:Macrophages D050296:Microbial Viability D009504:Neutrophils D010587:Phagocytosis D011014:Pneumonia
L-ficolin Aspergillus fumigatus epithelial macrophage neutrophil phagocytosis cytokines lung transplant