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During Aspergillus Infection, Monocyte-Derived DCs, Neutrophils, and Plasmacytoid DCs Enhance Innate Immune Defense

Yahui Guo1, Shinji Kasahara1, Anupam Jhingran1

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

Cell Host & Microbe
|June 3, 2020
PubMed

Insights

Plasmacytoid dendritic cells (pDCs) amplify neutrophil responses against Aspergillus fumigatus lung infections. These antiviral cells are crucial for host defense by enhancing neutrophil antifungal activity.

Area of Science:

  • Immunology
  • Mycology
  • Infectious Diseases

Background:

  • Invasive aspergillosis (IA) is a serious threat to immunocompromised individuals.
  • Host defense against IA involves neutrophils and monocyte-derived dendritic cells (Mo-DCs).
  • Plasmacytoid dendritic cells (pDCs), known for antiviral roles, are investigated for their function in antifungal immunity.

Purpose of the Study:

  • To investigate the role of pDCs in host defense against Aspergillus fumigatus lung infection.
  • To elucidate the mechanisms by which pDCs are recruited to the lungs during aspergillosis.
  • To determine the functional contribution of pDCs to antifungal immunity.

Main Methods:

  • Murine model of Aspergillus fumigatus lung infection.
  • Analysis of immune cell recruitment (pDCs, neutrophils, Mo-DCs) using flow cytometry and chemokine signaling.
  • Targeted pDC ablation to assess their necessity for host defense.
  • Assessment of neutrophil function, including NADPH oxidase activity and fungal killing.

Main Results:

  • Aspergillus-infected Mo-DCs and neutrophils recruited pDCs to the lungs via CXCL9 and CXCL10 signaling.
  • pDC recruitment was dependent on Dectin-1, Card9, and type I/III interferon signaling.
  • Targeted pDC ablation revealed their essential role in host defense against IA.
  • pDCs enhanced neutrophil-mediated killing of Aspergillus conidia without direct interaction.

Conclusions:

  • pDCs are critical components of the innate immune response to inhaled Aspergillus fumigatus conidia.
  • pDCs act as amplifiers of neutrophil effector functions, enhancing antifungal immunity.
  • pDCs represent a novel therapeutic target for invasive aspergillosis.
Keywords:
Aspergillus fumigatusCXCL10CXCL9CXCR3fungusinnate immunitylungmonocyte-derived dendritic cellneutrophilplasmacytoid DC

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