Enhancement of macrophage candidacidal activity by interferon-γ: Increased phagocytosis, killing, and calcium signal mediated by a decreased number of mannose receptors

L. Máródi, Stefan Schreiber, Donald C. Anderson, Richard P. MacDermott, Helen M. Korchak, Richard B. Johnston

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

In contrast to its macrophage-activating capacity, IFN-γ downregulates expression of the macrophage mannose receptor (MMR), which mediates uptake of Candida and other microorganisms. We found that IFN-γ induced a concentration-dependent increase in the capacity of human monocyte-derived macrophages to ingest and kill both opsonized and unopsonized Candida albicans and to release Superoxide anion upon stimulation with Candida. Mannan or mannosylated albumin inhibited this activated uptake of unopsonized Candida, but glucan did not. Addition of mAb to complement receptor (CR) 3 did not inhibit ingestion; macrophages that lacked CR3 (leukocyte adhesion defect) showed normal upregulation of ingestion by IFN-γ. The increased candidacidal activity of IFN-γ-activated macrophages was associated with reduced expression of MMR by a mean of 79% and decreased pinocytic uptake of 125I-mannosylated BSA by 73%; ATuptake of pinocytosis was not changed. Exposure of resident macrophages to unopsonized Candida did not elicit a transient increase in intracellular free Ca2+ ([Ca2+]i); macrophages activated by IFN-γ expressed a brisk increase in [Ca2+]i on exposure to Candida. These data suggest that macrophage activation by IFN-γ can enhance resistance to C. albicans infection in spite of downregulation of the MMR, perhaps through enhanced coupling of the MMR to microbicidal functions.

Original languageEnglish
Pages (from-to)2596-2601
Number of pages6
JournalJournal of Clinical Investigation
Volume91
Issue number6
Publication statusPublished - Jun 1993

Fingerprint

Phagocytosis
Interferons
Macrophages
Calcium
Candida
Candida albicans
Down-Regulation
Eating
mannose receptor
Macrophage-1 Antigen
Pinocytosis
Mannans
Glucans
Macrophage Activation
Superoxides
Albumins
Leukocytes
Up-Regulation
Infection

Keywords

  • Calcium
  • Candida
  • Interferon-γ
  • Macrophages
  • Mannose receptor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Enhancement of macrophage candidacidal activity by interferon-γ : Increased phagocytosis, killing, and calcium signal mediated by a decreased number of mannose receptors. / Máródi, L.; Schreiber, Stefan; Anderson, Donald C.; MacDermott, Richard P.; Korchak, Helen M.; Johnston, Richard B.

In: Journal of Clinical Investigation, Vol. 91, No. 6, 06.1993, p. 2596-2601.

Research output: Contribution to journalArticle

Máródi, L. ; Schreiber, Stefan ; Anderson, Donald C. ; MacDermott, Richard P. ; Korchak, Helen M. ; Johnston, Richard B. / Enhancement of macrophage candidacidal activity by interferon-γ : Increased phagocytosis, killing, and calcium signal mediated by a decreased number of mannose receptors. In: Journal of Clinical Investigation. 1993 ; Vol. 91, No. 6. pp. 2596-2601.
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