Glycosphingolipids mediate Pneumocystis cell wall β-glucan activation of the IL-23/IL-17 axis in human dendritic cells

Eva M. Carmona, Theodore J. Kottom, Deanne M. Hebrink, Teng Moua, Raman Deep Singh, Andrew H. Limper

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Pneumocystis species are opportunistic fungal organisms that cause severe pneumonia in immune-compromised hosts, with resultant high morbidity and mortality. Recent work indicates that IL-17 responses are important components of host defense against fungal pathogens. In the present study, we demonstrate that cell surface β-glucan components of Pneumocystis (PCBG) stimulate human dendritic cells (DCs) to secrete IL-23 and IL-6. These cytokines are well established to stimulate a T helper-17 (Th17) phenotype. Accordingly, we further observe that PCBG-stimulated human DCs interact with lymphocytes to drive the secretion of IL-17 and IL-22, both Th17-produced cytokines. The activation of DCs was shown to involve the dectin-1 receptor with a downstream activation of the Syk kinase and subsequent translocation of both the canonical and noncanonical components of the NF-κB transcription factor family. Finally, we demonstrate that glycosphingolipid-rich microdomains of the plasma membrane participate in the activation of DCs by PCBG through the accumulation of lactosylceramide at the cell surface during stimulation with PCBG. These data strongly support the idea that the β-glucan surface components of Pneumocystis drive the activation of the IL-23/IL-17 axis during this infection, through a glycosphingolipid-initiated mechanism.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume47
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Dendritic cells
  • IL-17
  • IL-23
  • Pneumocystis
  • β-glucan

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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