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Normal human fibroblasts express pattern recognition receptors for fungal (1-->3)-beta-D-glucans

P Kougias1, D Wei, P J Rice

  • 1Departments of Surgery, James H. Quillen College of Medicine, Johnson City, Tennessee 37614, USA.

Infection and Immunity
|May 12, 2001
PubMed

Insights

Fungal (1-->3)-beta-D-glucans bind to human dermal fibroblasts, activating immune pathways. This discovery reveals that glucan recognition extends beyond immune cells, impacting skin cell function.

Area of Science:

  • Immunology
  • Dermatology
  • Molecular Biology

Background:

  • Fungal cell wall glucans are known innate immunity stimulants, primarily acting through immune cells like macrophages, neutrophils, and NK cells.
  • The existence of glucan receptors on non-immune cells has not been previously reported.
  • Understanding fungal-host interactions is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the presence and characteristics of glucan binding sites on normal human dermal fibroblasts (NHDF).
  • To determine if glucans can modulate the functional activity of NHDF.
  • To explore the implications of glucan-fibroblast interactions in host-fungal recognition.

Main Methods:

  • Primary cultures of normal human dermal fibroblasts (NHDF) were used.
  • Saturable binding assays were performed to quantify glucan binding.
  • Competition studies with glucan phosphate and laminarin were conducted.
  • NF-kappaB nuclear binding activity and IL-6 gene expression were measured.

Main Results:

  • NHDF membranes showed saturable binding of a water-soluble glucan with a dissociation constant (K(D)) of 8.9 μg/ml.
  • Competition studies indicated at least two distinct glucan binding sites on NHDF.
  • Glucan stimulation led to time-dependent activation of NF-kappaB and increased IL-6 mRNA levels in fibroblasts.
  • This study is the first to report glucan binding sites and functional modulation on human fibroblasts.

Conclusions:

  • Human dermal fibroblasts possess pattern recognition receptors for fungal (1-->3)-beta-D-glucans.
  • Glucans can directly influence the functional activity of fibroblasts, suggesting a broader role in host-fungal interactions.
  • These findings expand the understanding of host recognition of fungal components beyond the immune system.

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