Impaired blood dendritic cell numbers and functions after aneurysmal subarachnoid hemorrhage.
Portions of this study were presented at the Annual Congress of Société Française d'Anesthésie et de Réanimation in Paris, September 2012.


BACKGROUND
Toll-like receptor (TLR) agonists are promising therapy for the prevention of nosocomial infections in critical ill patients. We aimed to analyze the TLR-reactivity of circulating dendritic cells (DC) as assessed by cytokine production after an ex vivo challenge with TLR agonists in aneurysmal subarachnoid hemorrhage (SAH) patients.


RESULTS
A single-center prospective observational study took place in one intensive care unit of a teaching hospital. Blood samples were harvested on days 2, 5 and 10 in 21 severe SAH patients requiring mechanical ventilation and 17 healthy controls. DC production of cytokines (Tumour Necrosis Factor, TNF-α; Interleukin, IL-12; and Interferon, IFN-α) was assessed by intracellular immunostaining on TLR-3, 4, 7/8 and 9 stimulations. SAH patients had decreased numbers of blood myeloid (mDCs) and plasmacytoid DCs (pDCs) on days 2, 5 and 10. Compared with the healthy controls, the frequency of mDCs producing TNF-α after TLR-3 stimulation was decreased in the SAH patients. The frequency of myeloid DCs producing IL-12 after TLR-3 and 4 stimulations was also decreased in the SAH patients. In contrast, the mDCs response to TLR-7/8 was not impaired in the SAH patients. The frequency of pDCs producing TNF-α(+) and IFN-α(+) on TLR-7/8 stimulation were reduced at all of the tested times in the SAH patients, whereas reactivity to TLR-9 was preserved. On day 2, the pDCs from non-survivor patients (n=8) had a decreased ability to produce IFN-α on TLR-9 stimulation compared with the survivors.


CONCLUSIONS
These data suggest functional abnormalities of circulating pDCs and mDCs that could be important for immunomodulation after SAH.
Laboratoire UPRES EA 3826 "Thérapeutiques cliniques et expérimentales des infections", Faculté de Médecine, Université de Nantes, Nantes, France.
Antoine
A
Roquilly
Cécile
C
Braudeau
Raphael
R
Cinotti
Erwan
E
Dumonte
Rémi
R
Motreul
Régis
R
Josien
Karim
K
Asehnoune
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D061251:Primary Cell Culture; D011446:Prospective Studies; D011804:Quinolines / Q000494:pharmacology; D012121:Respiration, Artificial; D013345:Subarachnoid Hemorrhage / Q000378:metabolism / Q000473:pathology*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
C547051:CL097 compound; C527702:CpG ODN 2395; D016207:Cytokines; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D011804:Quinolines; D051193:Toll-Like Receptors; D011070:Poly I-C