PMID- 22885107
OWN - NLM
STAT- MEDLINE
DCOM- 20130206
LR  - 20171116
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 181
IP  - 4
DP  - 2012 Oct
TI  - Dendritic cells are central coordinators of the host immune response to 
      Staphylococcus aureus bloodstream infection.
PG  - 1327-37
LID - S0002-9440(12)00521-4 [pii]
LID - 10.1016/j.ajpath.2012.06.039 [doi]
AB  - Dendritic cells (DCs) play an important role in integration of the immune 
      responses induced by pathogens. The purpose of this study was to determine the 
      importance of DCs in host defense against Staphylococcus aureus bacteremia. Using 
      a murine infection model, we demonstrated that DCs are rapidly recruited into 
      infected tissue after intravenous inoculation with S. aureus. The recruited DCs 
      were fully functional and in a more advanced stage of maturation than those 
      isolated from uninfected mice. Depletion of DCs in CD11c-DTR transgenic mice 
      resulted in substantial worsening of infection, as indicated by increased 
      bacterial loads in kidneys and lungs, accelerated mortality, and more severe 
      pathology. Furthermore, DC depletion completely abolished IL-12 production in 
      response to infection. The beneficial effect afforded by DCs during S. aureus 
      infection was not mediated by their contribution to direct bacterial killing, nor 
      by increased neutrophil recruitment. Instead, neutrophil influx (along with 
      expression of CXC chemokines) was significantly enhanced in infected tissue after 
      depletion of DCs. We also found that the bactericidal capacity of the recruited 
      neutrophils was significantly impaired in DC-depleted mice. More importantly, the 
      detrimental effect of DC depletion was practically reversed by treatment with 
      exogenous recombinant mouse IL-12. Our results demonstrated that DCs, probably 
      through their production of IL-12, play an important role in coordinating the 
      inflammatory response during S. aureus infection.
CI  - Copyright (c) 2012 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Schindler, Daniela
AU  - Schindler D
AD  - Infection Immunology Research Group, Helmholtz Centre for Infection Research, 
      Germany.
FAU - Gutierrez, Maximiliano G
AU  - Gutierrez MG
FAU - Beineke, Andreas
AU  - Beineke A
FAU - Rauter, Yvonne
AU  - Rauter Y
FAU - Rohde, Manfred
AU  - Rohde M
FAU - Foster, Simon
AU  - Foster S
FAU - Goldmann, Oliver
AU  - Goldmann O
FAU - Medina, Eva
AU  - Medina E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120810
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CD11c Antigen)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Bacteremia/blood/complications/microbiology/pathology
MH  - CD11c Antigen/metabolism
MH  - Dendritic Cells/*immunology/microbiology/pathology/ultrastructure
MH  - Host-Pathogen Interactions/drug effects/*immunology
MH  - Immunity/drug effects/*immunology
MH  - Inflammation/blood/complications/pathology
MH  - Interleukin-12/administration & dosage/metabolism/pharmacology
MH  - Lung/drug effects/immunology/microbiology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Microbial Viability/drug effects
MH  - Neutrophil Infiltration/drug effects
MH  - Phagocytosis/drug effects
MH  - Spleen/drug effects/immunology/microbiology/pathology
MH  - Staphylococcal Infections/*blood/complications/*immunology/microbiology
MH  - Staphylococcus aureus/drug effects/growth & 
      development/*immunology/ultrastructure
EDAT- 2012/08/14 06:00
MHDA- 2013/02/07 06:00
CRDT- 2012/08/14 06:00
PHST- 2012/02/28 00:00 [received]
PHST- 2012/05/06 00:00 [revised]
PHST- 2012/06/14 00:00 [accepted]
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/02/07 06:00 [medline]
AID - S0002-9440(12)00521-4 [pii]
AID - 10.1016/j.ajpath.2012.06.039 [doi]
PST - ppublish
SO  - Am J Pathol. 2012 Oct;181(4):1327-37. doi: 10.1016/j.ajpath.2012.06.039. Epub 
      2012 Aug 10.