Porcine Neonatal Blood Dendritic Cells, but Not Monocytes, Are More Responsive to TLRs Stimulation than Their Adult Counterparts

Gael Auray,Jill Van Kessel,Rachelle Buchanan,Volker Gerdts,Lorne A Babiuk,Marina R Facci,Mauricio Martins Rodrigues

doi:10.1371/journal.pone.0059629

Gael Auray, Jill Van Kessel + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0059629

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Journal: PloS one	Publication Date: May 8, 2013
Citations: 77	License type: CC BY 4.0

Affiliation: University of Saskatchewan, University of Alberta

Abstract

The neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs) play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response. As pigs are becoming more important for vaccine development studies due to their similarity to the human immune system, we decided to compare the activation and maturation of a subpopulation of porcine DCs in adult and neonatal pigs following stimulation with different TLR ligands, which are promising candidates for adjuvants in vaccine formulations. Porcine blood derived DCs (BDCs) were directly isolated from blood and consisted of a mix of conventional and plasmacytoid DCs. Following CpG ODN (TLR9 ligand) and imiquimod (TLR7 ligand) stimulation, neonatal BDCs showed higher levels of expression of costimulatory molecules and similar (CpG ODN) or higher (imiquimod) levels of IL-12 compared to adult BDCs. Another interesting feature was that only neonatal BDCs produced IFN-α after TLR7 or TLR9 ligand stimulation. Stimulation with CpG ODN and imiquimod also induced enhanced expression of several chemokines. Moreover, in a mixed leukocyte reaction assay, neonatal BDCs displayed a greater ability to induce lymphoproliferation. These findings suggest that when stimulated via TLR7 or TLR9 porcine DCs display similar if not better response than adult porcine DCs.

Highlights

Antigen presenting cells (APCs), by sampling antigens and presenting them to immune cells, play a key role in the development of the adaptive immune response
None of the Toll like receptors (TLR) ligands used induced a significant upregulation of costimulatory molecules at the surface of adult or neonatal monocytes compared to non stimulated cells, even though imiquimod and class A CpG ODN seemed to induce a slight upregulation in neonates compared to adults (Figure 1B)
When supernatants were tested for cytokine production, we found that LPS induced TNF-a production by adult monocytes but not by neonatal monocytes (Figure 1C)

Summary

Introduction

Antigen presenting cells (APCs), by sampling antigens and presenting them to immune cells, play a key role in the development of the adaptive immune response. APCs are present in peripheral tissues and especially at mucosal surface where they sample antigens Upon encountering pathogens, they reach a mature state through triggering of their Pattern Recognition Receptors (PRRs) by highly conserved Molecular Associated Molecular Patterns (MAMPs). DCs migrate to lymph nodes to activate T helper (Th) cells and drive the immune response towards a Th1, Th2, Th17 or Treg type of response [3,4]. This unique ability to activate naive T cells and tailor the immune response makes DCs a target of choice for vaccine formulations. Very little is known about the activation and maturation of porcine neonatal DCs

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