Serum opsonin ficolin-A enhances host-fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following Aspergillus fumigatus challenge.
Invasive aspergillosis is a devastating invasive fungal disease associated with a high mortality rate in the immunocompromised, such as leukaemia patients, transplant patients and those with HIV/AIDS. The rodent serum orthologue of human L-ficolin, ficolin-A, can bind to and opsonize Aspergillus fumigatus, the pathogen that causes invasive aspergillosis, and may participate in fungal defence. Using human monocyte-derived macrophages and neutrophils isolated from healthy donors, we investigated conidial association and fungal viability by flow cytometry and microscopy. Additionally, cytokine production was measured via cytometric bead arrays. Ficolin-A opsonization was observed to significantly enhance association of conidia, while also inhibiting hyphal growth and contributing to increased fungal killing following incubation with monocyte-derived macrophages and neutrophils. Additionally, ficolin-A opsonization was capable of manifesting a decrease in IL-8, IL-1β, IL-6, IL-10 and TNF-α production from MDM and IL-1β, IL-6 and TNF-α from neutrophils 24 h post-infection. In conclusion, rodent ficolin-A is functionally comparable to human L-ficolin and is capable of modulating the innate immune response to A. fumigatus, down-regulating cytokine production and could play an important role in airway immunity.
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.|Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Stefan
S
Bidula
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.|School of Pharmacy and Biomolecular Science, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Darren W
DW
Sexton
Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. sschelenz@doctors.org.uk.|Department of Microbiology, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. sschelenz@doctors.org.uk.
Silke
S
Schelenz
D001228:Aspergillosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D037102:Lectins / Q000097:blood*; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D050296:Microbial Viability / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D000097604:Ficolins
D016207:Cytokines; D018836:Inflammation Mediators; D037102:Lectins; D000097604:Ficolins
Aspergillosis; Cytokines; Innate immunity; Macrophage; Neutrophil