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. 2016 Apr;205(2):133-42. doi: 10.1007/s00430-015-0435-9. Epub 2015 Sep 4.

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.

Keywords: Aspergillosis; Cytokines; Innate immunity; Macrophage; Neutrophil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillosis / immunology*
  • Aspergillosis / metabolism*
  • Aspergillosis / microbiology
  • Aspergillus fumigatus / immunology*
  • Cytokines / metabolism*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Inflammation Mediators / metabolism
  • Lectins / blood*
  • Leukocytes / immunology*
  • Leukocytes / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Microbial Viability / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Lectins
  • ficolin