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Puttur F.,Helmholtz Center for Infection Research | Arnold-Schrauf C.,Helmholtz Center for Infection Research | Lahl K.,Stanford University | Solmaz G.,Helmholtz Center for Infection Research | And 11 more authors.
PLoS Pathogens | Year: 2013

Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon α (IFNα), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H+ pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies. © 2013 Puttur et al.

Tamoutounour S.,Aix - Marseille University | Tamoutounour S.,French Institute of Health and Medical Research | Tamoutounour S.,French National Center for Scientific Research | Guilliams M.,Aix - Marseille University | And 35 more authors.
Immunity | Year: 2013

In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and Tcell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate Tcells. Conventional dermal DCs excelled both at migrating and activating Tcells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6Chi monocytes. Their Tcell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic Tcells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin. © 2013 Elsevier Inc.

Yona S.,Weizmann Institute of Science | Yona S.,University College London | Kim K.-W.,Weizmann Institute of Science | Kim K.-W.,Yale University | And 14 more authors.
Immunity | Year: 2013

Mononuclear phagocytes, including monocytes, macrophages, and dendritic cells, contribute to tissue integrity as well as to innate and adaptive immune defense. Emerging evidence for labor division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organization of this cellular network are not well defined. Here we report a fate-mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX3CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue-resident macrophage populations, including liver Kupffer cells and lung alveolar, splenic, and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that short-lived Ly6C+ monocytes constitute obligatory steady-state precursors of blood-resident Ly6C- cells and that the abundance of Ly6C+ blood monocytes dynamically controls the circulation lifespan of their progeny. © 2013 Elsevier Inc.

Lambrecht B.N.,Laboratory of Immunoregulation and Mucosal Immunology | Lambrecht B.N.,Ghent University | Lambrecht B.N.,Erasmus Medical Center | Hammad H.,Laboratory of Immunoregulation and Mucosal Immunology
Annual Review of Immunology | Year: 2012

Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious stimuli. Lung DCs are heavily influenced by the nearby epithelial cells, and a model is emerging whereby direct communication between DCs and epithelial cells determines the outcome of the pulmonary immune response. Here, we have approached DC biology from the perspective of viral infection and allergy to illustrate these emerging concepts. © 2012 by Annual Reviews. All rights reserved.

Neyt K.,Laboratory of Immunoregulation and Mucosal Immunology | Neyt K.,Erasmus University Rotterdam | Perros F.,Ghent University | GeurtsvanKessel C.H.,French Institute of Health and Medical Research | And 5 more authors.
Trends in Immunology | Year: 2012

The lymph nodes (LNs) and spleen have an optimal structure that allows the interaction between T cells, B cells and antigen-presenting dendritic cells (DCs) on a matrix made up by stromal cells. Such a highly organized structure can also be formed in tertiary lymphoid organs (TLOs) at sites of infection or chronic immune stimulation. This review focuses on the molecular mechanisms of TLO formation and maintenance, the controversies surrounding the nature of the inducing events, and the functions of these structures in infection, transplantation and autoimmunity. © 2012 Elsevier Ltd.

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