Secreted pH-regulated antigen 1 of Candida albicans blocks activation and conversion of complement C3

The Journal of Immunology : Official Journal of the American Association of Immunologists
Shanshan LuoPeter F Zipfel

Abstract

The complement system forms the first defense line of innate immunity and is activated within seconds upon infection by human pathogenic yeast Candida albicans. In this study, we identified a new complement evasion strategy used by C. albicans. The fungus secretes a potent complement inhibitor, pH-regulated Ag 1 (Pra1), which in the direct surrounding of the pathogen binds to fluid-phase C3 and blocks cleavage of C3 to C3a and C3b, as shown by ELISA, native gel electrophoresis, and Western blotting. Consequently, complement activation via the alternative and classical pathways is inhibited. In addition, the release of the anaphylatoxins C3a and C5a, as well as C3b/iC3b surface deposition, is reduced, as demonstrated by Western blotting, ELISA, confocal microscopy, and flow cytometry. By reducing C3b/iC3b levels at the yeast surface, Pra1 decreases complement-mediated adhesion, as well as uptake of C. albicans by human macrophages, as shown by flow cytometry. Thus, Pra1 is, to our knowledge, the first potent fungal complement inhibitor that favors C. albicans immune escape by inactivating and controlling host complement attack at the level of C3.

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Citations

Mar 28, 2012·The Journal of Biological Chemistry·Diana BarthelPeter F Zipfel
Jan 19, 2012·Infection and Immunity·Shih-Chin ChengMihai G Netea
Jul 5, 2012·PLoS Pathogens·Francesco CitiuloDuncan Wilson
Mar 16, 2017·Molecular Plant-microbe Interactions : MPMI·Chengjian XieXingyong Yang
Apr 26, 2012·European Journal of Immunology·Peter F Zipfel, Christine Skerka
Apr 26, 2012·European Journal of Immunology·Shih-Chin ChengMihai G Netea
Jan 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Teresia HallströmKristian Riesbeck
Nov 30, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diana BarthelPeter F Zipfel
Jan 29, 2013·Medical Microbiology and Immunology·Pedro MiramónBernhard Hube
Apr 2, 2020·Frontiers in Cellular and Infection Microbiology·Dhirendra Kumar SinghAttila Gácser
Nov 30, 2016·Frontiers in Cellular and Infection Microbiology·Caroline M MarcosAna M Fusco-Almeida
Oct 6, 2020·Frontiers in Immunology·Alexander TilleMarc Thilo Figge
Jan 27, 2018·Journal of Fungi·Marco J Hernández-ChávezHéctor M Mora-Montes
Sep 27, 2019·Frontiers in Immunology·Namarta KaliaManpreet Kaur
Jul 1, 2020·Current Opinion in Microbiology·Sarah DellièreVishukumar Aimanianda

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