Candida albicans recognition by and escape from macrophages

• Main Author: McKenzie, Christopher Gordon Jemison
• Published: University of Aberdeen 2011
• Subjects: 616.9; Candida Albicans : Macrophages
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542642

Disruption of <i>N-</i>mannosylation and <i>O</i>-mannosylation on the <i>C. albicans</i> outer cell wall increased the rate by which <i>C. albicans</i> is ingested by macrophages. Conversely, disruption of phosphomannosylation reduced the rate of <i>C. albicans</i> is phagocytosis. Alterations to the outer cell wall and genetic or chemical inhibition of hyphal morphogenesis in <i>C. albicans</i> resulted in significantly abrogated macrophage killing <i>in vitro</i>. Disruption of <i>C. albicans </i>ability to tolerate oxidative stresses also perturbed its ability to escape from and kill macrophages. The engagement of specific receptors on the macrophage surface is an essential component of <i>C. albicans</i> recognition and clearance. In the presence of serum, blocking pattern recognition receptors associated with specific fungal cell wall epitopes (Mannose Receptor, Dectin 1 and CD16/32) resulted in an initial decrease in phagocytosis and decreased macrophage killing. Blocking macrophage pattern recognition receptors using soluble components of the<i> C. albicans</i> cell wall resulted in decreased phagocytosis under serum free conditions of <i>O-</i>linked mannans only, and reduced macrophage killing for macrophages pre-exposed to <i>N-</i>mannan and laminarin. The presence of serum increased the rate of uptake for macrophages pre-exposed to <i>N-</i>mannan and laminarin, and had no affect upon macrophage killing. The interaction of <i>C. albicans</i> cell wall epitopes with macrophage pattern recognition receptors, coupled with <i>C. albicans</i> ability to respond to stresses encountered after ingestion are critical determinants of the macrophage’s ability to ingest and process <i>C. albicans.</i>