CpG-ODN and MPLA prevent mortality in a murine model of post-hemorrhage-Staphyloccocus aureus pneumonia.
Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8(+) cDCs- and CD8(-) cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia.
Laboratoire UPRES EA 3826 Thérapeutiques cliniques et expérimentales des infections, Faculté de médecine, Université de Nantes, Nantes, France.
Antoine
A
Roquilly
Laetitia
L
Gautreau
Jean Pierre
JP
Segain
Pierre
P
de Coppet
Véronique
V
Sebille
Cédric
C
Jacqueline
Jocelyne
J
Caillon
Gilles
G
Potel
Corinne
C
Lejus
Régis
R
Josien
Karim
K
Asehnoune
D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010865:Pilot Projects; D018410:Pneumonia, Bacterial / Q000150:complications / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D012771:Shock, Hemorrhagic / Q000150:complications*; D013211:Staphylococcus aureus / Q000302:isolation & purification*; D013601:T-Lymphocytes / Q000473:pathology
C408982:CPG-oligonucleotide; D016207:Cytokines; D008050:Lipid A; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C048436:monophosphoryl lipid A