Immune cells fold and damage fungal hyphae

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment,...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 118; no. 15; pp. 1 - 8
Main Authors Bain, Judith M., Alonso, M. Fernanda, Childers, Delma S., Walls, Catriona A., Mackenzie, Kevin, Pradhan, Arnab, Lewis, Leanne E., Louw, Johanna, Avelar, Gabriela M., Larcombe, Daniel E., Netea, Mihai G., Gow, Neil A. R., Brown, Gordon D., Erwig, Lars P., Brown, Alistair J. P.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 13.04.2021
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Summary:Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans–macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin–myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.
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1Present address: Medical Department, Roche International Ltd., 11300 Montevideo, Uruguay.
Author contributions: J.M.B., D.S.C., C.A.W., A.P., L.E.L., J.L., G.M.A., D.E.L., M.G.N., N.A.R.G., G.D.B., L.P.E., and A.J.P.B. designed research; J.M.B., M.F.A., L.E.L., and C.A.W performed research; K.M. and G.D.B. contributed new reagents/analytic tools; J.M.B., N.A.R.G., L.P.E., and A.J.P.B. analyzed data; J.M.B. and A.J.P.B. wrote the paper; and D.S.C., C.A.W., K.M., A.P., J.L., G.M.A., D.E.L., M.G.N., N.A.R.G., G.D.B., and L.P.E. edited the paper.
Edited by Amariliz Rivera, Rutgers New Jersey Medical School, Newark, NJ, and accepted by Editorial Board Member Carl F. Nathan February 20, 2021 (received for review September 30, 2020)
2Present address: Division of Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2020484118