CANDIDACIDAL MECHANISMS IN THE HUMAN NEONATE - IMPAIRED IFN-GAMMA ACTIVATION OF MACROPHAGES IN NEWBORN-INFANTS

We studied the interaction between Candida albicans and mononuclear ph agocytes derived from cord blood. in the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived mac rophages was equivalent for newborns and adults. In the absence of ser um both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and m annan inhibited ingestion of unopsonized candida by macrophages, sugge sting a role for the mannose receptor. Exposure of cord and adult macr ophages to IFN-gamma (10-500 U/ml) gave quantitatively different resul ts in Candida killing, as well as in release of superoxide anion (O-2( -)). Maximal increase in these functions with adult macrophages was ac hieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages c ould be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O-2(-) release compared with adult cells. Defective up-regulation of O-2(-) release was also prese nt in cord monocytes exposed to IFN-gamma on day 0. Studies of the sur face expression of IFN-gamma receptors using a ''nonblocking'' mAb aga inst the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, the re was a three times higher number of positive cells in cord monocytes . Specific binding of I-125-IFN-gamma to cord monocytes and macrophage s was also higher compared with adult cells. These data suggest that n eonatal macrophages have a normal capacity to ingest and kill both ops onized and unopsonized Candida but cannot be fully activated by IFN-ga mma, a finding that could not be attributed to lower expression of IFN -gamma receptors on the neonatal cells.