PMID- 23189191
OWN - NLM
STAT- MEDLINE
DCOM- 20130516
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Burn injury triggered dysfunction in dendritic cell response to TLR9 activation 
      and resulted in skewed T cell functions.
PG  - e50238
LID - 10.1371/journal.pone.0050238 [doi]
LID - e50238
AB  - Severe trauma such as burn injury is often associated with a systemic 
      inflammatory syndrome characterized by a hyperactive innate immune response and 
      suppressed adaptive immune function. Dendritic cells (DCs), which sense pathogens 
      via their Toll-like receptors (TLRs), play a pivotal role in protecting the host 
      against infections. The effect of burn injury on TLR-mediated DC function is a 
      debated topic and the mechanism controlling the purported immunosuppressive 
      response remains to be elucidated. Here we examined the effects of burn injury on 
      splenic conventional DC (cDC) and plasmacytoid DC (pDC) responses to TLR9 
      activation. We demonstrate that, following burn trauma, splenic cDCs' cytokine 
      production profile in response to TLR9 activation became anti-inflammatory 
      dominant, with high production of IL-10 (>50% increase) and low production of 
      IL-6, TNF-alpha and IL-12p70 ( approximately 25-60% reduction). CD4+ T cells activated by these 
      cDCs were defective in producing Th1 and Th17 cytokines. Furthermore, burn injury 
      had a more accentuated effect on pDCs than on cDCs. Following TLR9 activation, 
      pDCs displayed an immature phenotype with an impaired ability to secrete 
      pro-inflammatory cytokines (IFN-alpha, IL-6 and TNF-alpha) and to activate T cell 
      proliferation. Moreover, cDCs and pDCs from burn-injured mice had low transcript 
      levels of TLR9 and several key molecules of the TLR signaling pathway. Although 
      hyperactive innate immune response has been associated with severe injury, our 
      data show to the contrary that DCs, as a key player in the innate immune system, 
      had impaired TLR9 reactivity, an anti-inflammatory phenotype, and a dysfunctional 
      T cell-priming ability. We conclude that burn injury induced impairments in DC 
      immunobiology resulting in suppression of adaptive immune response. Targeted DC 
      immunotherapies to promote their ability in triggering T cell immunity may 
      represent a strategy to improve immune defenses against infection following burn 
      injury.
FAU - Shen, Haitao
AU  - Shen H
AD  - Department of Cell Biology and Human Anatomy, University of California Davis, 
      Davis, California, United States of America.
FAU - de Almeida, Patricia E
AU  - de Almeida PE
FAU - Kang, Kyung H
AU  - Kang KH
FAU - Yao, Pamela
AU  - Yao P
FAU - Chan, Camie W
AU  - Chan CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121126
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - Burns/genetics/*immunology/*metabolism
MH  - Cell Differentiation
MH  - Cytokines/biosynthesis/immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Inflammation Mediators/immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Signal Transduction
MH  - Spleen/cytology/immunology/metabolism
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Th1 Cells/cytology/immunology/metabolism
MH  - Th17 Cells/cytology/immunology/metabolism
MH  - Toll-Like Receptor 9/genetics/*metabolism
PMC - PMC3506591
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/11/29 06:00
MHDA- 2013/05/17 06:00
PMCR- 2012/11/26
CRDT- 2012/11/29 06:00
PHST- 2012/06/30 00:00 [received]
PHST- 2012/10/22 00:00 [accepted]
PHST- 2012/11/29 06:00 [entrez]
PHST- 2012/11/29 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
PHST- 2012/11/26 00:00 [pmc-release]
AID - PONE-D-12-19305 [pii]
AID - 10.1371/journal.pone.0050238 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e50238. doi: 10.1371/journal.pone.0050238. Epub 2012 Nov 26.