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Serum opsonin ficolin-A enhances host–fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following Aspergillus fumigatus challenge

Abstract

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.

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Acknowledgments

We are grateful to Dr. Orla Jupp (University of East Anglia), for processing blood and providing us with monocytes and neutrophils. We would also like to thank Prof. Russell Wallis and Dr. Umakhanth Venkatraman Girija for supplying us with recombinant rat ficolin-A. This work was supported by a Faculty of Health, University of East Anglia, UK Ph.D. studentship (FMH 04.4.66 C4).

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Correspondence to Silke Schelenz.

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Bidula, S., Sexton, D.W. & Schelenz, S. Serum opsonin ficolin-A enhances host–fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following Aspergillus fumigatus challenge. Med Microbiol Immunol 205, 133–142 (2016). https://doi.org/10.1007/s00430-015-0435-9

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Keywords

  • Aspergillosis
  • Macrophage
  • Neutrophil
  • Cytokines
  • Innate immunity