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Immunological down-regulation of host defenses in fungal infections

J W Murphy1

  • 1Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, USA. juneann-murphy@ouhsc.edu

Mycoses
|June 24, 2000
PubMed

Insights

Cryptococcus neoformans evades host defenses using its capsule, which inhibits immune cell migration and promotes fungal virulence. This pathogen effectively down-regulates both innate and adaptive immune responses, leading to severe infections.

Area of Science:

  • Mycology
  • Immunology
  • Pathogenesis

Background:

  • Fungal pathogens employ virulence factors to establish progressive disease.
  • Cryptococcus neoformans (Cr. neoformans) is a significant human pathogen causing cryptococcosis.
  • Cr. neoformans can evade and suppress host immune responses, contributing to its virulence.

Purpose of the Study:

  • To elucidate the mechanisms by which Cr. neoformans down-regulates host protective mechanisms.
  • To investigate the role of the fungal capsule in immune evasion and pathogenesis.

Main Methods:

  • Analysis of the Cr. neoformans capsule's role in inhibiting phagocytosis.
  • Investigation of capsular polysaccharide effects on leukocyte migration (L-selectin shedding).
  • Assessment of capsular polysaccharide-induced regulatory T cell activity.

Main Results:

  • The Cr. neoformans capsule inhibits phagocytosis and causes L-selectin shedding from leukocytes, reducing immune cell infiltration.
  • Intravascular capsular polysaccharides induce regulatory T cells, suppressing cell-mediated immunity.
  • Highly virulent isolates exhibit excessive capsular material production, correlating with immune down-modulation.

Conclusions:

  • Cr. neoformans utilizes its capsule as a key virulence factor to evade host defenses.
  • The down-regulation of innate and adaptive immunity by the capsular polysaccharide is critical for Cr. neoformans pathogenesis.
  • Targeting these immune evasion strategies could offer therapeutic benefits against cryptococcosis.

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