Candidacidal mechanisms in the human neonate: Impaired IFN-γ activation of macrophages in newborn infants

L. Máródi, Rita Káposzta, Donald E. Campbell, Richard A. Polin, József Csongor, Richard B. Johnston

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Abstract

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-γ (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-γ. 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-γ on day 0. Studies of the surface expression of IFN-γ receptors using a 'nonblocking' mAb against the IFN-γ 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-γ 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-γ, a finding that could not be attributed to lower expression of IFN-γ receptors on the neonatal cells.

Original languageEnglish
Pages (from-to)5643-5649
Number of pages7
JournalJournal of Immunology
Volume153
Issue number12
Publication statusPublished - Dec 15 1994

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Macrophage Activation
Macrophages
Newborn Infant
Candida
Monocytes
Phagocytosis
Mannans
Phagocytes
Serum
Candida albicans
Fetal Blood
Superoxides
Up-Regulation
Cell Count
Eating

ASJC Scopus subject areas

  • Immunology

Cite this

Máródi, L., Káposzta, R., Campbell, D. E., Polin, R. A., Csongor, J., & Johnston, R. B. (1994). Candidacidal mechanisms in the human neonate: Impaired IFN-γ activation of macrophages in newborn infants. Journal of Immunology, 153(12), 5643-5649.

Candidacidal mechanisms in the human neonate : Impaired IFN-γ activation of macrophages in newborn infants. / Máródi, L.; Káposzta, Rita; Campbell, Donald E.; Polin, Richard A.; Csongor, József; Johnston, Richard B.

In: Journal of Immunology, Vol. 153, No. 12, 15.12.1994, p. 5643-5649.

Research output: Contribution to journalArticle

Máródi, L, Káposzta, R, Campbell, DE, Polin, RA, Csongor, J & Johnston, RB 1994, 'Candidacidal mechanisms in the human neonate: Impaired IFN-γ activation of macrophages in newborn infants', Journal of Immunology, vol. 153, no. 12, pp. 5643-5649.
Máródi L, Káposzta R, Campbell DE, Polin RA, Csongor J, Johnston RB. Candidacidal mechanisms in the human neonate: Impaired IFN-γ activation of macrophages in newborn infants. Journal of Immunology. 1994 Dec 15;153(12):5643-5649.
Máródi, L. ; Káposzta, Rita ; Campbell, Donald E. ; Polin, Richard A. ; Csongor, József ; Johnston, Richard B. / Candidacidal mechanisms in the human neonate : Impaired IFN-γ activation of macrophages in newborn infants. In: Journal of Immunology. 1994 ; Vol. 153, No. 12. pp. 5643-5649.
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