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Eur J Immunol. 2015 Oct;45(10):2821-33. doi: 10.1002/eji.201545530. Epub 2015 Jul 24.

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

Author information

  • 1Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
  • 2Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
  • 3Instituto de Investigaciones Biotecnológicas-(IIB-INTECH), Universidad Nacional de San Martín-CONICET, Argentina.
  • 4Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
  • 5NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
  • 6Microbiology Institute - Clinical Microbiology, Immunology, and Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Germany.
  • 7Department of Dermatology, University of Tübingen, Tübingen, Germany.
  • 8Department of Pharmacology and Experimental Therapy, Institute for Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
  • 9Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.

Abstract

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.

KEYWORDS:

Bacterial infection; Dendritic cells; IFN-γ; Monocytes; Sepsis

PMID:
26138432
DOI:
10.1002/eji.201545530
[PubMed - indexed for MEDLINE]
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