Abstract
Dendritic cells (DCs) are a component of the placental immune system, but their role in pregnancy is still poorly understood. Decidual DCs (dDCs) were selected from at-term pregnancy on the basis of CD14 and CD11c expression. A phenotypic analysis revealed that dDCs are characterized by the expression of monocyte-derived DC (moDCs) markers and specific markers such as HLA-G and its ligand ILT4. As demonstrated by whole-genome microarray, dDCs expressed a specific gene program markedly distinct from that of moDCs; it included estrogen- and progesterone-regulated genes and genes encoding immunoregulatory cytokines, which is consistent with the context of foeto-maternal tolerance. A functional analysis of dDCs showed that they were unable to mature in response to bacterial ligands such as lipopolysaccharide or peptidoglycan, as assessed by the expression of HLA-DR, CD80, CD83, and CD86. When dDCs were incubated with bacteria known for their placenta tropism, Coxiella burnetii and Brucella abortus, they were also unable to mature and to produce inflammatory cytokines. It is likely that the defective maturation of dDCs and their inability to produce inflammatory cytokines is related to the spontaneous release of IL-10 by these cells. Taken together, these results suggest that dDCs exhibit an immunoregulatory program, which may favor the pathogenicity of C. burnetii or B. abortus.
Highlights
Dendritic cells (DCs) are sentinels that instruct the adaptive immune system at the interface of the host with environment
It is likely that the defective maturation of Decidual DCs (dDCs) and their inability to produce inflammatory cytokines is related to the spontaneous release of IL-10 by these cells. These results suggest that dDCs exhibit an immunoregulatory program, which may favor the pathogenicity of C. burnetii or B. abortus
The spontaneous secretion of IL-10 combined with the defective production of inflammatory cytokines likely accounts for the immunoregulatory profile of dDCs. These results suggest that dDCs play an immunoregulatory role in feto-maternal tolerance, which is not broken down by C. burnetii and B. abortus and may contribute to their pathogenicity
Summary
Dendritic cells (DCs) are sentinels that instruct the adaptive immune system at the interface of the host with environment. The maturation program of DCs includes loss of endocytosis ability, dramatic changes in surface markers such as CD80, CD83, CD86, and membrane translocation of MHC class II molecules. DCs are able to present the antigen to resting T cells (Banchereau and Steinman, 1998). The maturation program of DCs can be induced by microbial components such as lipopolysaccharide (LPS) and peptidoglycan (PGN) and modulated by the cytokine context. Interferon (IFN)-γ or Tumor Necrosis Factor (TNF) drive inflammatory activation while interleukin (IL)-4, IL-10, or Transforming Growth Factor (TGF)-β induce an immunoregulatory response of DCs. interferon (IFN)-γ or Tumor Necrosis Factor (TNF) drive inflammatory activation while interleukin (IL)-4, IL-10, or Transforming Growth Factor (TGF)-β induce an immunoregulatory response of DCs This leads to Th1 or Th2 response, respectively (Akdis et al, 2012; Dzopalic et al, 2012). Skin DCs are composed of epidermal Langerhans cells and different subtypes of dermal DCs that favor cell-mediated and antibody-mediated responses (Von Bubnoff et al, 2004; Kaplan et al, 2005; He et al, 2006)
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