PMID- 22927979
OWN - NLM
STAT- MEDLINE
DCOM- 20130129
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Caspase-2-dependent dendritic cell death, maturation, and priming of T cells in 
      response to Brucella abortus infection.
PG  - e43512
LID - 10.1371/journal.pone.0043512 [doi]
LID - e43512
AB  - Smooth virulent Brucella abortus strain 2308 (S2308) causes zoonotic brucellosis 
      in cattle and humans. Rough B. abortus strain RB51, derived from S2308, is a live 
      attenuated cattle vaccine strain licensed in the USA and many other countries. 
      Our previous report indicated that RB51, but not S2308, induces a 
      caspase-2-dependent apoptotic and necrotic macrophage cell death. Dendritic cells 
      (DCs) are professional antigen presenting cells critical for bridging innate and 
      adaptive immune responses. In contrast to Brucella-infected macrophages, here we 
      report that S2308 induced higher levels of apoptotic and necrotic cell death in 
      wild type bone marrow-derived DCs (WT BMDCs) than RB51. The RB51 and 
      S2308-induced BMDC cell death was regulated by caspase-2, indicated by the 
      minimal cell death in RB51 and S2308-infected BMDCs isolated from caspase-2 
      knockout mice (Casp2KO BMDCs). More S2308 bacteria were taken up by Casp2KO BMDCs 
      than wild type BMDCs. Higher levels of S2308 and RB51 cells were found in 
      infected Casp2KO BMDCs compared to infected WT BMDCs at different time points. 
      RB51-infected wild type BMDCs were mature and activated as shown by significantly 
      up-regulated expression of CD40, CD80, CD86, MHC-I, and MHC-II. RB51 induced the 
      production of cytokines TNF-alpha, IL-6, IFN-gamma and IL12/IL23p40 in infected BMDCs. 
      RB51-infected WT BMDCs also stimulated the proliferation of CD4(+) and CD8(+) T 
      cells compared to uninfected WT BMDCs. However, the maturation, activation, and 
      cytokine secretion are significantly impaired in Casp2KO BMDCs infected with RB51 
      or Salmonella (control). S2308-infected WT and Casp2KO BMDCs were not activated 
      and could not induce cytokine production. These results demonstrated that 
      virulent smooth strain S2308 induced more apoptotic and necrotic dendritic cell 
      death than live attenuated rough vaccine strain RB51; however, RB51, but not its 
      parent strain S2308, induced caspase-2-mediated DC maturation, cytokine 
      production, antigen presentation, and T cell priming.
FAU - Li, Xinna
AU  - Li X
AD  - Unit for Laboratory Animal Medicine and Department of Microbiology and 
      Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United 
      States of America.
FAU - He, Yongqun
AU  - He Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120822
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Vaccines, Attenuated)
RN  - EC 3.4.22.- (Caspase 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/*immunology
MH  - Bone Marrow Cells/cytology
MH  - Brucella abortus/cytology/immunology/*physiology
MH  - Caspase 2/*metabolism
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*cytology/immunology/metabolism/*microbiology
MH  - Female
MH  - Mice
MH  - Necrosis/immunology
MH  - Species Specificity
MH  - T-Lymphocytes/cytology/*immunology/metabolism/*microbiology
MH  - Vaccines, Attenuated/immunology
PMC - PMC3425542
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/29 06:00
MHDA- 2013/01/30 06:00
PMCR- 2012/08/22
CRDT- 2012/08/29 06:00
PHST- 2012/04/02 00:00 [received]
PHST- 2012/07/23 00:00 [accepted]
PHST- 2012/08/29 06:00 [entrez]
PHST- 2012/08/29 06:00 [pubmed]
PHST- 2013/01/30 06:00 [medline]
PHST- 2012/08/22 00:00 [pmc-release]
AID - PONE-D-12-09413 [pii]
AID - 10.1371/journal.pone.0043512 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e43512. doi: 10.1371/journal.pone.0043512. Epub 2012 Aug 22.