Leucine-Rich Repeat Kinase 2 Controls the Ca2+ /Nuclear Factor of Activated T Cells/IL-2 Pathway during Aspergillus Non-Canonical Autophagy in Dendritic Cells

Frontiers in Immunology
Alicia Yoke Wei WongTeresa Zelante

Abstract

The Parkinson's disease-associated protein, Leucine-rich repeat kinase 2 (LRRK2), a known negative regulator of nuclear factor of activated T cells (NFAT), is expressed in myeloid cells such as macrophages and dendritic cells (DCs) and is involved in the host immune response against pathogens. Since, the Ca2+/NFAT/IL-2 axis has been previously found to regulate DC response to the fungus Aspergillus, we have investigated the role played by the kinase LRRK2 during fungal infection. Mechanistically, we found that in the early stages of the non-canonical autophagic response of DCs to the germinated spores of Aspergillus, LRRK2 undergoes progressive degradation and regulates NFAT translocation from the cytoplasm to the nucleus. Our results shed new light on the complexity of the Ca2+/NFAT/IL-2 pathway, where LRRK2 plays a role in controlling the immune response of DCs to Aspergillus.

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Citations

Mar 1, 2019·Medical Mycology·Alicia Yoke Wei WongTeresa Zelante
Dec 24, 2018·Biochemical Society Transactions·Kirsten Harvey, Tiago F Outeiro
Mar 27, 2020·Frontiers in Neuroscience·Diba Ahmadi Rastegar, Nicolas Dzamko
Dec 21, 2021·Genomics·Jing YanBaoliang Zhu

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Methods Mentioned

BETA
nuclear translocation
Transfection
enzyme-linked immunosorbent assay
ELISA
Protein assay
electrophoresis
PCR
flow cytometry
electron microscopy
transmission electron microscopy

Software Mentioned

Graphpad
ImageJ
[UNK]
Fluorview FV1000
Graphpad Prism
MxPro QPCR

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