Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis.

Nature Microbiology
Irene KyrmiziGeorgios Chamilos

Abstract

LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulating LAP upstream of Rubicon and the mechanism of melanin-induced inhibition of this pathway remain incompletely understood. Herein, we identify a Ca2+ signalling pathway that depends on intracellular Ca2+ sources from endoplasmic reticulum, endoplasmic reticulum-phagosome communication, Ca2+ release from phagosome lumen and calmodulin (CaM) recruitment, as a master regulator of Rubicon, the phagocyte NADPH oxidase NOX2 and other molecular components of LAP. Furthermore, we provide genetic evidence for the physiological importance of Ca2+-CaM signalling in aspergillosis. Finally, we demonstrate that Ca2+ sequestration by Aspergillus melanin inside the phagosome abrogates activation of Ca2+-CaM signalling to inhibit LAP. These findings reveal the important role of Ca2+-CaM signalling in antifungal immunity and identify an im...Continue Reading

References

Jan 1, 1988·Pigment Cell Research·A M Meyer zum Gottesberge
Oct 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·U C Dräger
Jan 1, 1984·Archives of Dermatological Research·H Takematsu, M Seiji
Oct 1, 1996·Archives of Ophthalmology·S NakamuraM Tamai
Jul 12, 2002·Journal of Neural Transmission·L ZeccaM Gallorini
Mar 8, 2003·Pigment Cell Research·M J HoogduijnA J Thody
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zulfiqar A MalikDavid J Kusner
Apr 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Randall G WorthAlan D Schreiber
Aug 20, 2003·The Journal of Experimental Medicine·Isabelle VergneVojo Deretic
Oct 4, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Martha K Cathcart
Jan 15, 2005·Pigment Cell Research·Yan Liu, John D Simon
Jan 25, 2007·Molecular Cell·Maria Høyer-HansenMarja Jäättelä
Jun 15, 2007·Bone Marrow Transplantation·L ScruccaF Aversa
Jun 15, 2007·British Journal of Cancer·M E PolakI A Cree
Jun 22, 2007·The Journal of Physical Chemistry. B·Lian Hong, John D Simon
May 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ben De PauwUNKNOWN National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group
Jul 16, 2008·The Journal of Biological Chemistry·Yi-Pin LinYung-Fu Chang
Apr 20, 2010·Journal of Leukocyte Biology·Paula Nunes, Nicolas Demaurex
Apr 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erin K KellyLionel B Ivashkiv
Jan 18, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natacha SteinckwichEric J Tschirhart
Feb 19, 2011·Micron : the International Research and Review Journal for Microscopy·Antje BiesemeierOliver Eibl
Mar 20, 2012·Molecular & Cellular Proteomics : MCP·François-Xavier Campbell-ValoisMichel Desjardins
Oct 9, 2012·Current Biology : CB·Paula NunesNicolas Demaurex
Jul 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Irene KyrmiziGeorgios Chamilos
Jan 28, 2014·Nature·Kristin WestphalenJahar Bhattacharya
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Antonella de LucaFrank L van de Veerdonk
Jun 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin VaethStefan Feske
Jul 16, 2015·Pigment Cell & Melanoma Research·Marco d'IschiaShosuke Ito
Sep 15, 2015·Cell Reports·Teresa ZelantePaola Ricciardi-Castagnoli
Oct 9, 2015·Journal of Cell Science·Daniele GuidoPaula Nunes

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Citations

Feb 12, 2019·Cellular Microbiology·Johannes WestmanGregory D Fairn
Jan 4, 2020·Cell Death and Differentiation·Matthew D KellerKen Cadwell
Nov 15, 2019·Clinical Microbiology Reviews·Jean-Paul Latgé, Georgios Chamilos
Jul 17, 2020·Frontiers in Cellular and Infection Microbiology·Chukwuemeka Samson AhamefuleWenxia Fang
May 10, 2020·Nature Communications·Samuel M GonçalvesAgostinho Carvalho
Mar 25, 2020·Applied Microbiology and Biotechnology·Helene C EisenmanCarolyn W McGrail
Dec 16, 2018·Cellular Microbiology·Isabel ValsecchiAnne Beauvais
Dec 31, 2020·Journal of Fungi·Leandro C D BredaSandro Rogério de Almeida
May 12, 2020·Fungal Biology·Silvia WehmeierAlexandra C Brand
Feb 2, 2021·FEMS Microbiology Reviews·Antonia LastBernhard Hube
Oct 5, 2018·Current Opinion in Immunology·Jennifer Martinez
Mar 16, 2021·Frontiers in Immunology·Jenny A Nguyen, Robin M Yates
Apr 4, 2021·Journal of Fungi·Sichen LiuJoshua D Nosanchuk
Jul 6, 2020·Trends in Biochemical Sciences·Nicolas PaponYves Delneste
Apr 20, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Anthony J MorganAntony Galione
Mar 24, 2021·Infection and Immunity·Divya ArunachalamDharmalingam Kuppamuthu
Jul 3, 2021·Cell Host & Microbe·Tonia AkoumianakiGeorgios Chamilos
Aug 16, 2021·Cellular Microbiology·Taiane N SouzaLeonardo Nimrichter

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Methods Mentioned

BETA
confocal microscopy
electron microscopy
flow cytometry
bronchoalveolar lavage
ELISA
electrophoresis
light microscopy
PCR

Software Mentioned

R
LCS Lite
Adobe Photoshop
FlowJo
LCS Lite software
cmprsk for
cmprsk

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