Differential Adaptation of Candida albicans In Vivo Modulates Immune Recognition by Dectin-1

PLoS Pathogens

Simon Vautier¹  Carol A. Munro¹  Louise A. Walker¹  Ann Kerrigan¹  Alistair J. P. Brown¹  Joanna Potrykus¹  Hector M. Mora-Montes¹  Neil A. R. Gow¹  Donna M. MacCallum¹  Kelly M. Shepardson²  Robert A. Cramer²  Gordon D. Brown³  Mohlopheni J. Marakalala³  Alex Hopke⁴  Robert Wheeler⁴  Mihai G. Netea⁵  Graeme I. Murray⁶ 

[1] Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom;Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America;Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa;Molecular and Biomedical Sciences, University of Maine, Orono, Maine, United States of America;Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and University Medical Centre Nijmegen, Nijmegen, The Netherlands;Pathology, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom

关键词: C;    ida albicans;    Cell walls;    Fungal diseases;    Chitin;    Kidneys;    Cytokines;    Fungal genetics;    Inflammation;   

DOI  :  10.1371/journal.ppat.1003315

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The β-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.

【 授权许可】

CC BY