PMID- 26385522
OWN - NLM
STAT- MEDLINE
DCOM- 20160401
LR  - 20181113
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 195
IP  - 9
DP  - 2015 Nov 1
TI  - Flt3 Ligand Is Essential for Survival and Protective Immune Responses during 
      Toxoplasmosis.
PG  - 4369-77
LID - 10.4049/jimmunol.1500690 [doi]
AB  - Dendritic cells (DCs) are critical for resistance to Toxoplasma gondii, and 
      infection with this pathogen leads to increased numbers of DCs at local sites of 
      parasite replication and in secondary lymphoid organs, but the factors that 
      regulate this expansion are poorly understood. The cytokine Flt3 ligand (Flt3L) 
      is critical for the generation and maintenance of DCs, and Flt3L(-/-) mice were 
      found to be highly susceptible to acute toxoplasmosis. This phenotype correlated 
      with decreased production of IL-12 and IFN-gamma, as well as impaired NK cell 
      responses. Surprisingly, despite low basal numbers of DCs, Flt3L(-/-) mice 
      infected with T. gondii displayed an expansion of CD8alpha(+) and CD11b(lo)CD8alpha(-) 
      DCs. Infection also induced an expansion of parasite-specific CD4(+) and CD8(+) T 
      cells in Flt3L(-/-) mice; however, these cells were reduced in number and 
      displayed impaired ability to produce IFN-gamma relative to wild-type controls. 
      Exogenous IL-12 treatment partially restored NK and T cell responses in 
      Flt3L(-/-) mice, as well as acute resistance; however, these mice eventually 
      succumbed to toxoplasmic encephalitis, despite the presence of large numbers of 
      DCs and T cells in the brain. These results highlight the importance of Flt3L for 
      resistance to toxoplasmosis and demonstrate the existence of Flt3L-independent 
      pathways that can mediate infection-induced expansion of DCs and T cell priming.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Dupont, Christopher D
AU  - Dupont CD
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Harms Pritchard, Gretchen
AU  - Harms Pritchard G
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Hidano, Shinya
AU  - Hidano S
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Christian, David A
AU  - Christian DA
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Wagage, Sagie
AU  - Wagage S
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Muallem, Gaia
AU  - Muallem G
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Tait Wojno, Elia D
AU  - Tait Wojno ED
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Hunter, Christopher A
AU  - Hunter CA
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104 chunter@vet.upenn.edu.
LA  - eng
GR  - R01 AI042334/AI/NIAID NIH HHS/United States
GR  - AI 41158/AI/NIAID NIH HHS/United States
GR  - T32 AI007532/AI/NIAID NIH HHS/United States
GR  - R01 AI041158/AI/NIAID NIH HHS/United States
GR  - AI 42334/AI/NIAID NIH HHS/United States
GR  - T32 DK007006/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150918
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adaptive Immunity/genetics/*immunology
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism/parasitology
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism/parasitology
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology/metabolism/parasitology
MH  - Flow Cytometry
MH  - Host-Parasite Interactions/immunology
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-12/immunology/metabolism
MH  - Killer Cells, Natural/immunology/metabolism/parasitology
MH  - Membrane Proteins/deficiency/genetics/*immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Survival Analysis
MH  - Toxoplasma/*immunology/physiology
MH  - Toxoplasmosis, Animal/*immunology/parasitology
PMC - PMC4610860
MID - NIHMS718157
EDAT- 2015/09/20 06:00
MHDA- 2016/04/02 06:00
PMCR- 2016/11/01
CRDT- 2015/09/20 06:00
PHST- 2015/04/14 00:00 [received]
PHST- 2015/08/20 00:00 [accepted]
PHST- 2015/09/20 06:00 [entrez]
PHST- 2015/09/20 06:00 [pubmed]
PHST- 2016/04/02 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - jimmunol.1500690 [pii]
AID - 10.4049/jimmunol.1500690 [doi]
PST - ppublish
SO  - J Immunol. 2015 Nov 1;195(9):4369-77. doi: 10.4049/jimmunol.1500690. Epub 2015 
      Sep 18.