PMID- 25200952
OWN - NLM
STAT- MEDLINE
DCOM- 20150107
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 8
DP  - 2014 Oct 15
TI  - Inflammation conditions mature dendritic cells to retain the capacity to present 
      new antigens but with altered cytokine secretion function.
PG  - 3851-9
LID - 10.4049/jimmunol.1303215 [doi]
AB  - Dendritic cells (DCs) are directly activated by pathogen-associated molecular 
      patterns (PAMPs) and undergo maturation. Mature DCs express high levels of MHC 
      class II molecules ("signal 1"), upregulate T cell costimulatory receptors 
      ("signal 2"), and secrete "signal 3" cytokines (e.g., IL-12). Mature DCs 
      efficiently present Ags linked to the activating PAMP and prime naive T cells. 
      However, mature DCs downregulate MHC II synthesis, which prevents them from 
      presenting newly encountered Ags. DCs can also be indirectly activated by 
      inflammatory mediators released during infection (e.g., IFN). Indirectly 
      activated DCs mature but do not present pathogen Ags (as they have not 
      encountered the pathogen) and do not provide signal 3. Therefore, although they 
      are probably generated in large numbers upon infection or vaccination, indirectly 
      activated DCs are considered to play little or no role in T cell immunity. In 
      this article, we show that indirectly activated DCs retain their capacity to 
      present Ags encountered after maturation in vivo. They can also respond to PAMPs, 
      but the previous encounter of inflammatory signals alters their cytokine (signal 
      3) secretion pattern. This implies that the immune response elicited by a PAMP is 
      more complex than predicted by the examination of the immunogenic features of 
      directly activated DCs, and that underlying inflammatory processes can skew the 
      immune response against pathogens. Our observations have important implications 
      for the design of vaccines and for the understanding of the interactions between 
      simultaneous infections, or of infection in the context of ongoing sterile 
      inflammation.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Vega-Ramos, Javier
AU  - Vega-Ramos J
AD  - Department of Microbiology and Immunology, Doherty Institute of Infection and 
      Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Walter 
      and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, 
      Australia;
FAU - Roquilly, Antoine
AU  - Roquilly A
AD  - Department of Microbiology and Immunology, Doherty Institute of Infection and 
      Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Surgical 
      Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, 
      France; and.
FAU - Zhan, Yifan
AU  - Zhan Y
AD  - Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, 
      Australia;
FAU - Young, Louise J
AU  - Young LJ
AD  - Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, 
      Australia;
FAU - Mintern, Justine D
AU  - Mintern JD
AD  - Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, 
      Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular 
      Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 
      3010, Australia.
FAU - Villadangos, Jose A
AU  - Villadangos JA
AD  - Department of Microbiology and Immunology, Doherty Institute of Infection and 
      Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Walter 
      and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, 
      Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular 
      Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 
      3010, Australia j.villadangos@unimelb.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140908
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD8 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.3.2.27 (MARCH1 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/*immunology
MH  - CD8 Antigens/biosynthesis
MH  - Cell Differentiation/immunology
MH  - Cytokines/*immunology
MH  - Dendritic Cells/*immunology
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Inflammation/*immunology
MH  - Inflammation Mediators/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Knockout
MH  - Ovalbumin/immunology
MH  - T-Lymphocytes/immunology
MH  - Toll-Like Receptor 9/genetics/immunology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Ubiquitin-Protein Ligases/biosynthesis
EDAT- 2014/09/10 06:00
MHDA- 2015/01/08 06:00
CRDT- 2014/09/10 06:00
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2015/01/08 06:00 [medline]
AID - jimmunol.1303215 [pii]
AID - 10.4049/jimmunol.1303215 [doi]
PST - ppublish
SO  - J Immunol. 2014 Oct 15;193(8):3851-9. doi: 10.4049/jimmunol.1303215. Epub 2014 
      Sep 8.