PMID- 19050269
OWN - NLM
STAT- MEDLINE
DCOM- 20090127
LR  - 20190516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 181
IP  - 12
DP  - 2008 Dec 15
TI  - Dendritic cells modulate lung response to Pseudomonas aeruginosa in a murine 
      model of sepsis-induced immune dysfunction.
PG  - 8513-20
AB  - Host infection by pathogens triggers an innate immune response leading to a 
      systemic inflammatory response, often followed by an immune dysfunction which can 
      favor the emergence of secondary infections. Dendritic cells (DCs) link innate 
      and adaptive immunity and may be centrally involved in the regulation of 
      sepsis-induced immune dysfunction. We assessed the contribution of DCs to lung 
      defense in a murine model of sublethal polymicrobial sepsis (cecal ligature and 
      puncture, CLP). In this model, bone marrow-derived DCs (BMDCs) retained an 
      immature phenotype, associated with decreased capacity of IL-12p70 release and 
      impaired priming of T cell lymphocytes. Eight days after CLP surgery, we induced 
      a secondary pulmonary infection through intratracheal instillation of 5 x 10(6) 
      CFUs of Pseudomonas aeruginosa. Whereas all sham-operated mice survived, 80% of 
      post-CLP mice died after secondary pneumonia. Post-CLP mice exhibited marked lung 
      damage with early recruitment of neutrophils, cytokine imbalance with decreased 
      IL-12p70 production, and increased IL-10 release, but no defective bacterial lung 
      clearance, while systemic bacterial dissemination was almost constant. 
      Concomitant intrapulmonary administration of exogenous BMDCs into post-CLP mice 
      challenged with P. aeruginosa dramatically improved survival. BMDCs did not 
      improve bacterial lung clearance, but delayed neutrophil recruitment, strongly 
      attenuated the early peak of TNF-alpha and restored an adequate Il-12p70/IL-10 
      balance in post-CLP mice. Thus, adoptive transfer of BMDCs reversed 
      sepsis-induced immune dysfunction in a relevant model of secondary P. aeruginosa 
      pneumonia. Unexpectedly, the mechanism of action of BMDCs did not involve 
      enhanced antibacterial activity, but occurred by dampening the pulmonary 
      inflammatory response.
FAU - Pene, Frederic
AU  - Pene F
AD  - Department of Cellular Biology, Centre National de la Recherche Scientifique, 
      Cochin Institute, University Paris-Descartes, Paris, France.
FAU - Zuber, Benjamin
AU  - Zuber B
FAU - Courtine, Emilie
AU  - Courtine E
FAU - Rousseau, Christophe
AU  - Rousseau C
FAU - Ouaaz, Fatah
AU  - Ouaaz F
FAU - Toubiana, Julie
AU  - Toubiana J
FAU - Tazi, Asmaa
AU  - Tazi A
FAU - Mira, Jean-Paul
AU  - Mira JP
FAU - Chiche, Jean-Daniel
AU  - Chiche JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/immunology/pathology
MH  - Cecum
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/*microbiology/transplantation
MH  - Disease Models, Animal
MH  - Female
MH  - Ligation
MH  - Lung/*immunology/*microbiology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Pneumonia, Bacterial/*immunology/*microbiology/mortality
MH  - Pseudomonas Infections/*immunology/*microbiology/mortality
MH  - Punctures
EDAT- 2008/12/04 09:00
MHDA- 2009/01/28 09:00
CRDT- 2008/12/04 09:00
PHST- 2008/12/04 09:00 [pubmed]
PHST- 2009/01/28 09:00 [medline]
PHST- 2008/12/04 09:00 [entrez]
AID - 181/12/8513 [pii]
AID - 10.4049/jimmunol.181.12.8513 [doi]
PST - ppublish
SO  - J Immunol. 2008 Dec 15;181(12):8513-20. doi: 10.4049/jimmunol.181.12.8513.