PMID- 22024399
OWN - NLM
STAT- MEDLINE
DCOM- 20120412
LR  - 20211020
IS  - 1471-2180 (Electronic)
IS  - 1471-2180 (Linking)
VI  - 11
DP  - 2011 Oct 24
TI  - Mycobacterium tuberculosis infection induces non-apoptotic cell death of human 
      dendritic cells.
PG  - 237
LID - 10.1186/1471-2180-11-237 [doi]
AB  - 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.
FAU - Ryan, Ruth C M
AU  - Ryan RC
AD  - Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College 
      Dublin, Ireland.
FAU - O'Sullivan, Mary P
AU  - O'Sullivan MP
FAU - Keane, Joseph
AU  - Keane J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111024
PL  - England
TA  - BMC Microbiol
JT  - BMC microbiology
JID - 100966981
RN  - 0 (Cytokines)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP7 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
SB  - IM
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - *Cell Death
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytokines/immunology
MH  - DNA Fragmentation
MH  - Dendritic Cells/immunology/*microbiology
MH  - Humans
MH  - Mycobacterium tuberculosis/*immunology
MH  - Phagocytosis
MH  - Tuberculosis/*immunology/microbiology
PMC - PMC3229477
EDAT- 2011/10/26 06:00
MHDA- 2012/04/13 06:00
PMCR- 2011/10/24
CRDT- 2011/10/26 06:00
PHST- 2011/03/11 00:00 [received]
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/10/26 06:00 [entrez]
PHST- 2011/10/26 06:00 [pubmed]
PHST- 2012/04/13 06:00 [medline]
PHST- 2011/10/24 00:00 [pmc-release]
AID - 1471-2180-11-237 [pii]
AID - 10.1186/1471-2180-11-237 [doi]
PST - epublish
SO  - BMC Microbiol. 2011 Oct 24;11:237. doi: 10.1186/1471-2180-11-237.