Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease

Stefanie S. V. Henriet, Jop Jans, Elles Simonetti, Kyung J. Kwon-Chung, Antonius J. M. M. Rijs, Peter W. M. Hermans, Steve M. Holland, Marien I. de Jonge, Adilia Warris

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16 Citations (Scopus)

Abstract

Invasive aspergillosis is a major threat to patients with chronic granulomatous disease (CGD). Fungal pathogenesis is the result of a diminished antifungal capacity and dysregulated inflammation. A deficient NADPH-oxidase complex results in defective phagolysosomal alkalization. To investigate the contribution of defective pH regulation in phagocytes among patients with CGD during fungal pathogenesis, we evaluated the effect of the acidotropic, antimalarial drug chloroquine (CQ) on the antifungal capacity of polymorphonuclear cells (PMNs) and on the inflammatory response of peripheral blood mononuclear cells (PBMCs). Chloroquine exerted a direct pH-dependent antifungal effect on Aspergillus fumigatus and Aspergillus nidulans; it increased the antifungal activity of PMNs from patients with CGD at a significantly lower concentration, compared with the concentration for PMNs from healthy individuals; and decreased the hyperinflammatory state of PBMCs from patients with CGD, as observed by decreased tumor necrosis factor α and interleukin 1β release. Chloroquine targets both limbs of fungal pathogenesis and might be of great value in the clearance of invasive aspergillosis in patients with CGD.
Original languageEnglish
Pages (from-to)1932-1939
Number of pages8
JournalThe journal of infectious diseases
Volume207
Issue number12
Early online date12 Mar 2013
DOIs
Publication statusPublished - 15 Jun 2013

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Keywords

  • antifungal agents
  • antimalarials
  • aspergillosis
  • Aspergillus fumigatus
  • Aspergillus nidulans
  • chloroquine
  • cytokines
  • dose-response relationship, drug
  • granulomatous disease, chronic
  • humans
  • hydrogen-Ion concentration
  • mmbrane glycoproteins
  • NADPH oxidase
  • phagocytes
  • phagosomes

Cite this

Henriet, S. S. V., Jans, J., Simonetti, E., Kwon-Chung, K. J., Rijs, A. J. M. M., Hermans, P. W. M., ... Warris, A. (2013). Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease. The journal of infectious diseases, 207(12), 1932-1939. https://doi.org/10.1093/infdis/jit103