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Efficient Method for Imaging Murine Lungs that Preserves Spatial Dynamics of Fungal Spores in the Airways
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Efficient Method for Imaging Murine Lungs that Preserves Spatial Dynamics of Fungal Spores in the Airways

Published on: December 13, 2024

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Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death

Neta Shlezinger1, Henriette Irmer2, Sourabh Dhingra3

  • 1Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Science (New York, N.Y.)
|September 9, 2017
PubMed

Insights

Lung neutrophils induce apoptosis-like death in Aspergillus conidia, preventing invasive fungal infections. An antiapoptotic protein, AfBIR1, is a key target for immune surveillance against this common mold pathogen.

Area of Science:

  • Immunology
  • Mycology
  • Cell Biology

Background:

  • Humans frequently inhale mold conidia, usually clearing them without symptoms.
  • Defective myeloid function can lead to conidial germination and invasive aspergillosis, but immune surveillance mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the mechanism of myeloid cell-mediated immune surveillance against Aspergillus conidia in the lung.
  • To identify fungal factors involved in evading host immune responses.

Main Methods:

  • In vivo monitoring of fungal physiology in a murine lung model.
  • Genetic manipulation of Aspergillus fumigatus to study the role of AfBIR1.
  • Pharmacologic inhibition of AfBIR1 activity.
  • Assessment of conidial susceptibility to NADPH oxidase-dependent killing.

Main Results:

  • Lung neutrophils induce programmed cell death with apoptosis-like features in Aspergillus conidia.
  • The antiapoptotic protein AfBIR1 inhibits fungal caspase activation and DNA fragmentation, promoting conidial survival.
  • AfBIR1 expression and activity correlate with conidial resistance to NADPH oxidase-dependent killing and host susceptibility to invasive aspergillosis.

Conclusions:

  • Host immune surveillance utilizes a fungal apoptosis-like programmed cell death pathway to control Aspergillus conidia.
  • Targeting AfBIR1 represents a potential strategy to enhance host immunity against invasive aspergillosis.

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