Dectin-1/IL-15 Pathway Affords Protection against Extrapulmonary Aspergillus fumigatus Infection by Regulating

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Fábio S Y Yoshikawa1, Maki Wakatsuki2, Kosuke Yoshida2

  • 1Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan, faseiti@gmail.com.

Journal of Innate Immunity
|January 19, 2023
PubMed

Insights

Mice lacking dectin-1 showed severe inflammation and succumbed to Aspergillus fumigatus infection. Dectin-1 protects against this fungal pathogen by preserving Natural Killer (NK) cells via Interleukin-15 (IL-15).

Area of Science:

  • Immunology
  • Mycology
  • Infectious Diseases

Background:

  • Aspergillus fumigatus is a common mold that can cause serious infections.
  • The immune system uses receptors like dectin-1 to detect fungal pathogens.
  • The precise immune mechanisms protecting against A. fumigatus are not fully understood.

Purpose of the Study:

  • To investigate the role of dectin-1 in the immune response to A. fumigatus.
  • To explore the immunological networks involved in anti-Aspergillus defense.

Main Methods:

  • Utilized a mouse model of acute invasive aspergillosis.
  • Compared the response of wild-type mice to mice lacking dectin-1.
  • Analyzed cytokine production, neutrophil infiltration, and immune cell populations (NK cells, T/B lymphocytes).

Main Results:

  • Mice lacking dectin-1 exhibited heightened inflammation, increased inflammatory cytokines, and neutrophil infiltration.
  • These dectin-1-deficient mice succumbed rapidly to infection.
  • Resistance was independent of T/B lymphocytes and IL-17.
  • Dectin-1's primary role involved preserving kidney Natural Killer (NK) cell populations through Interleukin-15 (IL-15).
  • NK cell depletion worsened host defense in wild-type mice.
  • IL-15 administration rescued antifungal responses in dectin-1-deficient mice.

Conclusions:

  • Dectin-1 plays a crucial role in anti-Aspergillus defense.
  • This receptor protects against invasive aspergillosis by maintaining NK cell numbers via IL-15.
  • Identified a novel dectin-1 effector mechanism in anti-fungal immunity.
Keywords:
Aspergillus fumigatusDectin-1IL-15NK cells

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