Innate immune system favors emergency monopoiesis at the expense of DC‐differentiation to control systemic bacterial infection in mice

• Published in: European journal of immunology Vol. 45; no. 10; pp. 2821 - 2833
• Main Authors: Pasquevich, Karina A., Bieber, Kristin, Günter, Manina, Grauer, Matthias, Pötz, Oliver, Schleicher, Ulrike, Biedermann, Tilo, Beer‐Hammer, Sandra, Bühring, Hans‐Jörg, Rammensee, Hans‐Georg, Zender, Lars, Autenrieth, Ingo B., Lengerke, Claudia, Autenrieth, Stella E.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2015
• Subjects: Animals; Bacteria; Bacterial infection; Bacterial infections; Cell Differentiation - immunology; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - pathology; IFN‐γ; Immune system; Immunity, Innate; Infections; Interferon-gamma - immunology; Mice; Mice, Knockout; Monocytes; Myelopoiesis - immunology; Pathogens; Rodents; Sepsis; Signal Transduction - immunology; T cell receptors; Toll-Like Receptor 4 - immunology; Yersinia enterocolitica; Yersinia enterocolitica - immunology; Yersinia Infections - immunology; Yersinia Infections - pathology; Bacterial infection; Sepsis; IFN-γ; Monocytes; Dendritic cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201545530

DCs are professional APCs playing a crucial role in the initiation of T‐cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC‐depletion in humans and mice. The mechanisms of pathogen‐induced DC‐depletion remain poorly understood. Previously, we showed that mice infected with Yersinia enterocolitica (Ye) had impaired de novo DC‐development, one reason for DC‐depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC‐depletion and the impact of different bacteria on DC‐development. We show that the number of bone marrow (BM) hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram‐positive and Gram‐negative bacteria. This is associated with a TLR4‐ and IFN‐γ−signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye‐infection. Adoptive transfer experiments revealed that infection‐induced monopoiesis occurs at the expense of DC‐development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC‐development leads to DC‐depletion, possibly driving transient immunosuppression in bacterial sepsis.