Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

Hdl Handle:
http://hdl.handle.net/10147/196271
Title:
Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells
Authors:
Ryan, Ruth CM; O'Sullivan, Mary P; Keane, Joseph
Citation:
BMC Microbiology. 2011 Oct 24;11(1):237
Issue Date:
24-Oct-2011
URI:
http://hdl.handle.net/10147/196271
Abstract:
Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorRyan, Ruth CM-
dc.contributor.authorO'Sullivan, Mary P-
dc.contributor.authorKeane, Joseph-
dc.date.accessioned2011-12-07T09:44:28Z-
dc.date.available2011-12-07T09:44:28Z-
dc.date.issued2011-10-24-
dc.identifierhttp://dx.doi.org/10.1186/1471-2180-11-237-
dc.identifier.citationBMC Microbiology. 2011 Oct 24;11(1):237-
dc.identifier.urihttp://hdl.handle.net/10147/196271-
dc.description.abstractAbstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.-
dc.titleMycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderRyan et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-12-02T16:07:41Z-
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.