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Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
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MDA5 Is an Essential Sensor of a Pathogen-Associated Molecular Pattern Associated with Vitality That Is Necessary for

Xi Wang1, Alayna K Caffrey-Carr1,2, Ko-Wei Liu1

  • 1Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.

Journal of Immunology (Baltimore, Md. : 1950)
|October 22, 2020
PubMed

Insights

The MDA5/MAVS pathway, part of RIG-I-like receptors, is crucial for fighting Aspergillus fumigatus lung infections by controlling immune cell responses and promoting neutrophil killing of fungal spores.

Area of Science:

  • Immunology
  • Mycology
  • Infectious Diseases

Background:

  • RIG-I-like receptors (RLRs) are key cytosolic sensors of viral RNA, primarily known for antiviral defense.
  • The role of RLRs in immunity against fungal pathogens like Aspergillus fumigatus is not well understood.

Purpose of the Study:

  • To investigate the role of MDA5/MAVS signaling in host defense against pulmonary Aspergillus fumigatus infection.
  • To elucidate the mechanisms by which MDA5/MAVS signaling contributes to antifungal immunity.

Main Methods:

  • Murine model of pulmonary Aspergillus fumigatus challenge.
  • Analysis of immune cell responses, including leukocyte and neutrophil activity.
  • Assessment of type I and type III interferon induction and signaling.
  • Detection of dsRNA from Aspergillus fumigatus.

Main Results:

  • MDA5/MAVS signaling is essential for host resistance against Aspergillus fumigatus.
  • Live Aspergillus fumigatus-derived dsRNA activates MDA5/MAVS signaling, acting as a vitality sensor.
  • MDA5/MAVS signaling differentially regulates type I and type III interferon production.
  • IFN-λ (type III) production is fully dependent on MDA5/MAVS, while IFN-α/β (type I) is partially dependent.
  • MDA5/MAVS-IFN axis drives CXCL10 expression and enhances neutrophil-mediated killing of Aspergillus fumigatus spores.

Conclusions:

  • The RIG-I-like receptor family, specifically MDA5/MAVS, plays a significant role in antifungal immunity.
  • MDA5/MAVS signaling is critical for orchestrating effective host defense against Aspergillus fumigatus lung infections.
  • This pathway broadens the known functions of RLRs beyond antiviral immunity.

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