In:
Infection and Immunity, American Society for Microbiology, Vol. 78, No. 4 ( 2010-04), p. 1650-1658
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 ( mmn4 Δ, pmr1 Δ, and mnt3 mnt5 Δ), whereas O- and N-linked mannan defects ( mnt1 Δ mnt2 Δ and mns1 Δ) 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 ( ece1 Δ, hwp1 Δ, and als3 Δ) and yeast-locked mutants ( clb2 Δ, hgc1 Δ, cph1 Δ, efg1 Δ, and efg1 Δ cph1 Δ), 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 .
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.00001-10
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2010
detail.hit.zdb_id:
1483247-1
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