title: Innate immune system favors emergency monopoiesis at the expense of DC-differentiation to control systemic bacterial infection in mice.
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.
authors.affiliation: Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.|Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.|Instituto de Investigaciones Biotecnológicas-(IIB-INTECH), Universidad Nacional de San Martín-CONICET, Argentina.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Pasquevich
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Bieber
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Manina
authors.initials: M
authors.lastname: Günter
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Grauer
authors.affiliation: NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pötz
authors.affiliation: Microbiology Institute - Clinical Microbiology, Immunology, and Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schleicher
authors.affiliation: Department of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.affiliation: Department of Pharmacology and Experimental Therapy, Institute for Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer-Hammer
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Zender
authors.affiliation: Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.affiliation: Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.|Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.|Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Autenrieth
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D015009:Yersinia Infections / Q000276:immunology* / Q000473:pathology; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma
keywords: Bacterial infection; Dendritic cells; IFN-γ; Monocytes; Sepsis