Pasquevich, Karina A. and Bieber, Kristin and Gunter, Manina and Grauer, Matthias and Potz, Oliver and Schleicher, Ulrike and Biedermann, Tilo and Beer-Hammer, Sandra and Buhring, Hans-Jörg and Rammensee, Hans-Georg and Zender, Lars and Autenrieth, Ingo B. and Lengerke, Claudia and Autenrieth, Stella E.. (2015) Innate immune system favors emergency monopoiesis at the expense of DC-differentiation to control systemic bacterial infection in mice. European Journal of Immunology, 45 (10). pp. 2821-2833.
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Official URL: https://edoc.unibas.ch/62314/
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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-gamma-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.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Stem Cells and Hematopoiesis (Lengerke) |
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UniBasel Contributors: | Lengerke, Claudia |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 1521-4141 (Electronic) 0014-2980 (Linking) |
Note: | Publication type according to Uni Basel Research Database: Journal article |
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Identification Number: |
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Last Modified: | 17 Nov 2018 14:34 |
Deposited On: | 17 Nov 2018 14:34 |
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