Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: A peroxisome proliferator-activated receptor-γ-mediated effect

Oleksii A. Skorokhod, Massimo Alessio, Benjamin Mordmüller, Paolo Arese, Evelin Schwarzer

Research output: Contribution to journalArticlepeer-review

Abstract

Acute and chronic Plasmodium falciparum malaria are accompanied by severe immunodepression possibly related to subversion of dendritic cells (DC) functionality. Phagocytosed hemozoin (malarial pigment) was shown to inhibit monocyte functions related to immunity. Hemozoin-loaded monocytes, frequently found in circulation and adherent to endothelia in malaria, may interfere with DC development and play a role in immunodepression. Hemozoin-loaded and unloaded human monocytes were differentiated in vitro to immature DC (iDC) by treatment with GM-CSF and IL-4, and to mature DC (mDC) by LPS challenge. In a second setting, hemozoin was fed to iDC further cultured to give mDC. In both settings, cells ingested large amounts of hemozoin undegraded during DC maturation. Hemozoin-fed monocytes did not apoptose but their differentiation and maturation to DC was severely impaired as shown by blunted expression of MHC class II and costimulatory molecules CD83, CD80, CD54, CD40, CD1a, and lower levels of CD83-specific mRNA in hemozoin-loaded iDC and mDC compared with unfed or latex-loaded DC. Further studies indicated activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) in hemozoin-loaded WC and mDC, associated with increased, expression of PPAR-γ mRNA, without apparent involvement of NF-κB. Moreover, expression of PPAR-γ was induced and up-regulation of CD83 was inhibited by supplementing iDC and mDC with plausible concentrations of 15(S)-hydroxyeicosatetraenoic acid, a PPAR-γ ligand abundantly produced by hemozoin via heme-catalyzed lipoperoxidation.

Original languageEnglish
Pages (from-to)4066-4074
Number of pages9
JournalJournal of Immunology
Volume173
Issue number6
Publication statusPublished - Sep 15 2004

ASJC Scopus subject areas

  • Immunology

Fingerprint

Dive into the research topics of 'Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: A peroxisome proliferator-activated receptor-γ-mediated effect'. Together they form a unique fingerprint.

Cite this