RT Journal Article
SR Electronic
T1 Toll-like receptor-4 agonist in post-haemorrhage pneumonia: role of dendritic and natural killer cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1365
OP 1378
DO 10.1183/09031936.00152612
VO 42
IS 5
A1 Antoine Roquilly
A1 Alexis Broquet
A1 Cedric Jacqueline
A1 Laetitia Gautreau
A1 Jean Pierre Segain
A1 Pierre de Coppet
A1 Jocelyne Caillon
A1 Frédéric Altare
A1 Regis Josien
A1 Karim Asehnoune
YR 2013
UL http://erj.ersjournals.com/content/42/5/1365.abstract
AB Haemorrhage-induced immunosuppression has been linked to nosocomial infections. We assessed the impact of monophosphoryl lipid A, a Toll/interleukin-1 receptor-domain-containing adaptor protein inducing interferon-biased Toll-like receptor-4 agonist currently used as a vaccine adjuvant in humans, on post-haemorrhage susceptibility to infection. We used a mouse model of post-haemorrhage pneumonia induced by methicillin-susceptible Staphylococcus aureus. Monophosphoryl lipid A was administered intravenously after haemorrhage and before pneumonia onset. Haemorrhage altered survival rate, increased lung damage (neutrophil accumulation, oedema and cytokine release) and altered the functions of dendritic and natural killer cells. Here, we show that monophosphoryl lipid A decreased systemic dissemination of S. aureus and dampened inflammatory lung lesions. Monophosphoryl lipid A partially restored the capacity for antigen presentation and the transcriptional activity in dendritic cells. Monophosphoryl lipid A did not restore the interferon-γ mRNA but prevented interleukin-10 mRNA overexpression in natural killer cells compared with untreated mice. Ex vivo monophosphoryl lipid A-stimulated dendritic cells or natural killer cells harvested from haemorrhaged animals were adoptively transferred into mice undergoing post-haemorrhage pneumonia. Stimulated dendritic cells (but not stimulated natural killer cells) improved the survival rate compared with mice left untreated. In vivo depletion of natural killer cells decreased survival rate of monophosphoryl lipid A-treated mice. Dendritic and natural killer cells are critically involved in the beneficial effects of monophosphoryl lipid A within post-haemorrhage pneumonia. Dendritic cells and NK cells are critically involved in the beneficial effects of MPLA within post-haemorrhage pneumonia http://ow.ly/oc4Zp