Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi

Roshanak Tolouei Semnani, Priyanka Goel Venugopal, Lily Mahapatra, Jason A. Skinner, Francoise Meylan, Daniel Chien, David W. Dorward, Damien Chaussabel, Richard M. Siegel, Thomas B. Nutman

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Abstract

Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24-96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, whereas mf exposure did not induce apoptosis in macrophages. Interestingly, 48-h exposure of DC to mf induced mRNA expression of the proapoptotic gene TRAIL and both mRNA and protein expression of TNF-α. mAb to TRAIL-R2, TNF-R1, or TNF-α partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. The mf also induced gene expression of BH3-interacting domain death agonist and protein expression of cytochrome c in DC; mf-induced cleavage of BH3-interacting domain death agonist could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-α-dependent fashion.

Original languageEnglish
Pages (from-to)7081-7089
Number of pages9
JournalJournal of Immunology
Volume181
Issue number10
Publication statusPublished - 15 Nov 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Semnani, R. T., Venugopal, P. G., Mahapatra, L., Skinner, J. A., Meylan, F., Chien, D., Dorward, D. W., Chaussabel, D., Siegel, R. M., & Nutman, T. B. (2008). Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi. Journal of Immunology, 181(10), 7081-7089.