Autophagy is redundant for the host defense against systemic Candida albicans infections

  • S. P. Smeekens
  • R. K. Malireddi
  • T. S. Plantinga
  • K. Buffen
  • M. Oosting
  • L. A. B. Joosten
  • B. J. Kullberg
  • J. R. Perfect
  • W. K. Scott
  • F. L. van de Veerdonk
  • R. J. Xavier
  • E. van de Vosse
  • T.-D. Kanneganti
  • M. D. Johnson
  • M. G. Netea
Article

DOI: 10.1007/s10096-013-2002-x

Cite this article as:
Smeekens, S.P., Malireddi, R.K., Plantinga, T.S. et al. Eur J Clin Microbiol Infect Dis (2014) 33: 711. doi:10.1007/s10096-013-2002-x

Abstract

Autophagy has been demonstrated to play an important role in the immunity against intracellular pathogens, but very little is known about its role in the host defense against fungal pathogens such as Candida albicans. Therefore, the role of autophagy for the host defense against C. albicans was assessed by complementary approaches using mice defective in autophagy, as well as immunological and genetic studies in humans. Although C. albicans induced LC3-II formation in macrophages, myeloid cell-specific ATG7−/− mice with defects in autophagy did not display an increased susceptibility to disseminated candidiasis. In in vitro experiments in human blood mononuclear cells, blocking autophagy modulated cytokine production induced by lipopolysaccharide, but not by C. albicans. Furthermore, autophagy modulation in human monocytes did not influence the phagocytosis and killing of C. albicans. Finally, 18 single-nucleotide polymorphisms in 13 autophagy genes were not associated with susceptibility to candidemia or clinical outcome of disease in a large cohort of patients, and there was no correlation between these genetic variants and cytokine production in either candidemia patients or healthy controls. Based on these complementary in vitro and in vivo studies, it can be concluded that autophagy is redundant for the host response against systemic infections with C. albicans.

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • S. P. Smeekens
    • 1
    • 2
  • R. K. Malireddi
    • 3
  • T. S. Plantinga
    • 1
    • 2
  • K. Buffen
    • 1
    • 2
  • M. Oosting
    • 1
    • 2
  • L. A. B. Joosten
    • 1
    • 2
  • B. J. Kullberg
    • 1
    • 2
  • J. R. Perfect
    • 4
  • W. K. Scott
    • 6
  • F. L. van de Veerdonk
    • 1
    • 2
  • R. J. Xavier
    • 7
    • 8
  • E. van de Vosse
    • 9
  • T.-D. Kanneganti
    • 3
  • M. D. Johnson
    • 4
    • 5
  • M. G. Netea
    • 1
    • 2
  1. 1.Department of MedicineRadboud university medical centerNijmegenThe Netherlands
  2. 2.Nijmegen Institute for Infection, Inflammation and Immunity (N4i)NijmegenThe Netherlands
  3. 3.Department of Immunology, St. Jude Children’s Research HospitalMemphisUSA
  4. 4.Division of Infectious Diseases and International HealthDuke University Medical CenterDurhamUSA
  5. 5.Campbell University College of Pharmacy and Health SciencesDurhamUSA
  6. 6.Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human GenomicsUniversity of Miami, Miller School of MedicineMiamiUSA
  7. 7.The Broad Institute of Massachusetts Institute of Technology and Harvard UniversityCambridgeUSA
  8. 8.Center for Computational and Integrative Biology and Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  9. 9.Department of Infectious DiseasesLeiden University Medical CenterLeidenThe Netherlands

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