Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants.
We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.
Maródi
L
L
Department of Pediatrics, University School of Medicine, Debrecen, Hungary.
Káposzta
R
R
Campbell
D E
DE
Polin
R A
RA
Csongor
J
J
Johnston
R B
RB
D000328:Adult; D002176:Candida albicans / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D017471:Receptors, Interferon / Q000276:immunology; D013481:Superoxides / Q000276:immunology; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D013481:Superoxides; D000096743:Interferon gamma Receptor