Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages.

L Marodi, HM Korchak… - Journal of immunology …, 1991 - journals.aai.org
L Marodi, HM Korchak, RB Johnston Jr
Journal of immunology (Baltimore, Md.: 1950), 1991journals.aai.org
We studied the biochemical basis of phagocytosis of Candida albicans, a serious pathogen,
and Candida parapsilosis, which is rarely pathogenic, by human monocytes (Mo) and
monocyte-derived macrophages (MDM). Optimal phagocytosis of both species by Mo
required the presence of extracellular Ca2+ and opsonization through both the classic and
alternative complement pathways. Serum-opsonized Candida were ingested equally by Mo
and MDM; unopsonized Candida were phagocytosed only by macrophages, and uptake …
Abstract
We studied the biochemical basis of phagocytosis of Candida albicans, a serious pathogen, and Candida parapsilosis, which is rarely pathogenic, by human monocytes (Mo) and monocyte-derived macrophages (MDM). Optimal phagocytosis of both species by Mo required the presence of extracellular Ca2+ and opsonization through both the classic and alternative complement pathways. Serum-opsonized Candida were ingested equally by Mo and MDM; unopsonized Candida were phagocytosed only by macrophages, and uptake began slowly. This opsonin-independent phagocytosis required Ca2+ and could be blocked by yeast mannan or mannose-BSA conjugate, suggesting a role for the mannose receptor. Opsonized Candida elicited a vigorous increase in the concentration of [Ca2+]i in Mo and MDM, but no Ca2+ transient was detected in MDM stimulated with unopsonized Candida. Pretreatment of MDM with ionomycin to increase [Ca2+]i had no effect on phagocytosis of unopsonized Candida. Addition of 5 mM EGTA completely inhibited changes in [Ca2+]i in Mo and MDM, suggesting that the Ca2+ transient induced by opsonized Candida is due to an influx of extracellular Ca2+. Differences in pathogenicity between the two Candida species could not be explained by differences in any aspect of phagocytosis. Uptake mediated by the macrophage mannose receptor could play a role in clearance of Candida under opsonin-poor conditions.
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