Contribution ofCandida albicansCell Wall Components to Recognition by and Escape from Murine Macrophages
- 1 April 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (4), 1650-1658
- https://doi.org/10.1128/iai.00001-10
Abstract
The pathogenicity of the opportunistic human fungal pathogenCandida albicansdepends 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 ofC. albicansinnate 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 ofC. albicansby macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4Δ,pmr1Δ, andmnt3 mnt5Δ), whereas O- and N-linked mannan defects (mnt1Δmnt2Δ andmns1Δ) 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 (ece1Δ,hwp1Δ, andals3Δ) and yeast-locked mutants (clb2Δ,hgc1Δ,cph1Δ,efg1Δ, andefg1Δcph1Δ), was similar to that observed for wild-typeC. 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 processC. albicans.Keywords
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