Blood components attenuate dendritic cell responses to TLR ligands in an in vitro model of transfusion — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. Blood components attenuate dendritic cell responses to TLR ligands in an in vitro model of transfusion

Blood components attenuate dendritic cell responses to TLR ligands in an in vitro model of transfusion (#198)

Melinda M Dean 1 2 , Katrina K Ki 1 3 , Helen M Faddy 1 3 , Lacey Johnson 4 , Denese Marks 4 , Robert L Flower 1 2
  1. Clinical Services and Research, Australian Red Cross Blood Service, Kelvin Grove, QLD, Australia
  2. Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
  3. School of Medicine, University of Queensland, St Lucia, QLD, Australia
  4. Clinical Services and Research, Australian Red Cross Blood Service, Alexandria, NSW, Australia

Background:

Transfusion of blood products has been reported to modulate patients’ immune responses; however the mechanisms remain largely unknown. Dendritic cells (DC) play an essential role at the interface of the innate and adaptive immune response. We hypothesised that blood transfusion modulates DC function and we focused on myeloid (m)DC and their BDCA3+ subset as important regulatory cells associated with transfusion-related immunomodulation.

 

Methods:

A human in vitro whole blood model of transfusion was utilised to assess the impact of packed red blood cells (PRBC), platelet concentrates (PC) and cryopreserved platelets (cryo-PLT) on mDC and BDCA3+ DC responses.  Following incubation of each blood component with ABO matched whole blood for 6hrs, changes in expression of mDC and BDCA3+ DC activation and co-stimulatory molecules (CD40, CD80, CD83, CD86) and production of inflammatory mediators (IL-6,TNF-α, IL-12, IL-10, IL-8, IP-10) were assessed  using  flow cytometry. In parallel, TLR agonists polyI:C or LPS were added  to model processes associated with viral or bacterial infection.

 

Results:

All three blood components modulated DC function. For both mDC and BDCA3+ DC, exposure to PRBC, PC or cryo-PLT resulted in a predominant suppression of activation and co-stimulatory molecules and suppressing cytokine and chemokine production. Importantly, in the models of concurrent infection, blood components attenuated mDC and BDCA3+ responses to TLR agonists.  Further, we found reduced BDCA3+ DC expression of CD80 combined with a reduction in IL-12 and IL-8 production as potential biomarkers associated with transfusion-associated immune modulation.

 

Conclusions:

Our research provides a comprehensive analysis of the impact of blood transfusion on the immune profile of DCs. We hypothesise that transfusion associated changes in DC  responses may result in a reduced capacity for signalling and communication with cells of the adaptive immune system resulting in failure to mount an appropriate immune response, particularly in the presence of an infectious complication.

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