PMID- 15604223
OWN - NLM
STAT- MEDLINE
DCOM- 20050607
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 9
DP  - 2005 May 1
TI  - Reversal of long-term sepsis-induced immunosuppression by dendritic cells.
PG  - 3588-95
AB  - Severe sepsis leads to long-term systemic and local immunosuppression, which is 
      the cause of a number of complications, including pulmonary infection. A 
      therapeutic strategy that reverses this immunosuppression is required, given the 
      ongoing high mortality rate of patients who have survived a severe sepsis. The 
      present study demonstrates that experimental severe sepsis renders the lung 
      susceptible to a normally innocuous Aspergillus fumigatus fungus challenge, due 
      to a dominant lung type 2 cytokine profile. Dendritic cells (DCs) obtained from 
      the lungs of mice subjected to cecal ligation and puncture (CLP) model were 
      skewed toward type 2 cytokine profile, which occurred with exaggerated expression 
      of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone 
      marrow-derived DCs (BMDCs) in postseptic mice prevented fatal Aspergillus 
      infection. This therapy reduced the overall inflammatory response and fungal 
      growth in the lung, and promoted the balance of proinflammatory and suppressive 
      cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore 
      the pulmonary host response in the postseptic lung in our animal model. These 
      data strongly suggest that lung DCs are profoundly affected as a consequence of 
      the systemic impact of severe sepsis, and the identification of mechanisms that 
      restore their function may serve as a key strategy to reverse sepsis-induced 
      immunosuppression.
FAU - Benjamim, Claudia F
AU  - Benjamim CF
AD  - Department of Pathology, University of Michigan, Medical School, 1301 Catherine 
      St, Ann Arbor, MI 48109-0602, USA.
FAU - Lundy, Steven K
AU  - Lundy SK
FAU - Lukacs, Nicholas W
AU  - Lukacs NW
FAU - Hogaboam, Cory M
AU  - Hogaboam CM
FAU - Kunkel, Steven L
AU  - Kunkel SL
LA  - eng
GR  - HL069865/HL/NHLBI NIH HHS/United States
GR  - HL31237/HL/NHLBI NIH HHS/United States
GR  - P50 HL60289/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041216
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Aspergillosis/immunology
MH  - Aspergillus fumigatus
MH  - Cytokines/immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Gene Expression Regulation/immunology
MH  - Green Fluorescent Proteins/genetics
MH  - *Immune Tolerance
MH  - Lung Diseases, Fungal/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Sepsis/*immunology/microbiology
MH  - Th2 Cells/immunology
PMC - PMC1895017
EDAT- 2004/12/18 09:00
MHDA- 2005/06/09 09:00
PMCR- 2006/05/01
CRDT- 2004/12/18 09:00
PHST- 2004/12/18 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2004/12/18 09:00 [entrez]
PHST- 2006/05/01 00:00 [pmc-release]
AID - S0006-4971(20)45554-5 [pii]
AID - 01053588 [pii]
AID - 10.1182/blood-2004-08-3251 [doi]
PST - ppublish
SO  - Blood. 2005 May 1;105(9):3588-95. doi: 10.1182/blood-2004-08-3251. Epub 2004 Dec 
      16.