Contribution of Candida albicans cell wall components to recognition by and escape from murine macrophages

C G J McKenzie, U Koser, L E Lewis, J M Bain, H M Mora-Montes, R N Barker, N A R Gow, L P Erwig

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The pathogenicity of the opportunistic human fungal pathogen Candida albicans depends on its ability to escape destruction by the host immune system. Using mutant strains that are defective in cell surface glycosylation, cell wall protein synthesis, and yeast-hypha morphogenesis, we have investigated three important aspects of C. albicans innate immune interactions: phagocytosis by primary macrophages and macrophage cell lines, hyphal formation within macrophage phagosomes, and the ability to escape from and kill macrophages. We show that cell wall glycosylation is critically important for the recognition and ingestion of C. albicans by macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4Delta, pmr1Delta, and mnt3 mnt5Delta), whereas O- and N-linked mannan defects (mnt1Delta mnt2Delta and mns1Delta) were associated with increased ingestion, compared to the parent wild-type strains and genetically complemented controls. In contrast, macrophage uptake of mutants deficient in cell wall proteins such as adhesins (ece1Delta, hwp1Delta, and als3Delta) and yeast-locked mutants (clb2Delta, hgc1Delta, cph1Delta, efg1Delta, and efg1Delta cph1Delta), was similar to that observed for wild-type C. albicans. Killing of macrophages was abrogated in hypha-deficient strains, significantly reduced in all glycosylation mutants, and comparable to wild type in cell wall protein mutants. The diminished ability of glycosylation mutants to kill macrophages was not a consequence of impaired hyphal formation within macrophage phagosomes. Therefore, cell wall composition and the ability to undergo yeast-hypha morphogenesis are critical determinants of the macrophage's ability to ingest and process C. albicans.
Original languageEnglish
Pages (from-to)1650-1658
Number of pages9
JournalInfection and Immunity
Volume78
Issue number4
Early online date1 Feb 2010
DOIs
Publication statusPublished - Apr 2010

Keywords

  • animals
  • candida albicans
  • cell line
  • cell survival
  • cell wall
  • cells, cultured
  • fungal proteins
  • glucans
  • hyphae
  • macrophages
  • mice
  • mice, inbred BALB C
  • phagocytosis
  • phagosomes

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