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 J. Chaussabel, Richard M. Siegel, Thomas B. Nutman

Research output: Contribution to journalArticle

21 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Brugia malayi
Microfilariae
Dendritic Cells
Monocytes
Apoptosis
Cytochromes c
BH3 Interacting Domain Death Agonist Protein
Cell Death
Macrophages
Receptors, Tumor Necrosis Factor, Type II
TNF-Related Apoptosis-Inducing Ligand Receptors
Gene Expression
Messenger RNA
Caspase 9
Caspases
Infection
Small Interfering RNA
Parasites
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Semnani, R. T., Venugopal, P. G., Mahapatra, L., Skinner, J. A., Meylan, F., Chien, D., ... 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.

Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi. / Semnani, Roshanak Tolouei; Venugopal, Priyanka Goel; Mahapatra, Lily; Skinner, Jason A.; Meylan, Francoise; Chien, Daniel; Dorward, David W.; Chaussabel, Damien J.; Siegel, Richard M.; Nutman, Thomas B.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7081-7089.

Research output: Contribution to journalArticle

Semnani, RT, Venugopal, PG, Mahapatra, L, Skinner, JA, Meylan, F, Chien, D, Dorward, DW, Chaussabel, DJ, Siegel, RM & Nutman, TB 2008, 'Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi', Journal of Immunology, vol. 181, no. 10, pp. 7081-7089.
Semnani RT, Venugopal PG, Mahapatra L, Skinner JA, Meylan F, Chien D et al. Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi. Journal of Immunology. 2008 Nov 15;181(10):7081-7089.
Semnani, Roshanak Tolouei ; Venugopal, Priyanka Goel ; Mahapatra, Lily ; Skinner, Jason A. ; Meylan, Francoise ; Chien, Daniel ; Dorward, David W. ; Chaussabel, Damien J. ; Siegel, Richard M. ; Nutman, Thomas B. / Induction of TRAIL- and TNF-α-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 7081-7089.
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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.",
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