PMID- 34233227 OWN - NLM STAT- MEDLINE DCOM- 20210831 LR - 20210831 IS - 1618-0607 (Electronic) IS - 1438-4221 (Linking) VI - 311 IP - 6 DP - 2021 Aug TI - Systemic bacterial infections affect dendritic cell development and function. PG - 151517 LID - S1438-4221(21)00046-1 [pii] LID - 10.1016/j.ijmm.2021.151517 [doi] AB - Dendritic cells (DCs) are critical in host defense against infection. DC depletion is an early event in the course of sepsis that may impair the host defense mechanisms. Here, we addressed whether DC depletion and dysfunction are pathogen-independent, mediated via pattern recognition receptors, and are due to impaired DC development upon systemic infection with the Gram-negative bacterium Escherichia coli and the Gram-positive pathogen Staphylococcus aureus. Infection with E. coli and S. aureus led to reduced numbers of splenic DC subsets and of DC progenitors in the bone marrow (BM) with this effect persisting significantly longer in mice infected with S. aureus than with E. coli. The reduction of DC subsets and their progenitors was mainly TLR-independent as was the infection-induced monopoiesis. Moreover, de novo DC development was impaired in mice infected with S. aureus, and BM cells from E. coli or S. aureus infected mice favored macrophage differentiation in vitro. As a consequence of reduced DC numbers and their reduced expression of MHC II less CD4(+) and CD8(+) T cells, especially Th1 and IFN-gamma producing CD8(+) T cells, could be detected in S. aureus compared to E. coli infected mice. These differences are reflected in the rapid killing of E. coli as opposed to an increase in bacterial load in S. aureus. In summary, our study supports the idea that systemic bacterial infections generally affect the number and development of DCs and thereby the T cell responses, but the magnitude is pathogen-dependent. CI - Copyright (c) 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Bieber, Kristin AU - Bieber K AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany. FAU - Gunter, Manina AU - Gunter M AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany; Research Group "Dendritic Cells in Infection and Cancer", German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Pasquevich, Karina A AU - Pasquevich KA AD - Instituto de Investigaciones Biotecnologicas-(IIBio), Universidad Nacional de San Martin-CONICET, Argentina. FAU - Autenrieth, Stella E AU - Autenrieth SE AD - Department of Internal Medicine II, University of Tubingen, Tubingen, Germany; Research Group "Dendritic Cells in Infection and Cancer", German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: Stella.Autenrieth@medizin.uni-tuebingen.de. LA - eng PT - Journal Article DEP - 20210630 PL - Germany TA - Int J Med Microbiol JT - International journal of medical microbiology : IJMM JID - 100898849 SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes MH - Cell Differentiation MH - Dendritic Cells MH - Escherichia coli MH - Mice MH - *Sepsis MH - *Staphylococcal Infections MH - Staphylococcus aureus OTO - NOTNLM OT - Dendritic cells OT - Development OT - Escherichia coli OT - Infection OT - Innate immune defense OT - Monocytes OT - Staphylococcus aureus OT - TLR EDAT- 2021/07/08 06:00 MHDA- 2021/09/01 06:00 CRDT- 2021/07/07 20:10 PHST- 2020/09/28 00:00 [received] PHST- 2021/04/29 00:00 [revised] PHST- 2021/06/25 00:00 [accepted] PHST- 2021/07/08 06:00 [pubmed] PHST- 2021/09/01 06:00 [medline] PHST- 2021/07/07 20:10 [entrez] AID - S1438-4221(21)00046-1 [pii] AID - 10.1016/j.ijmm.2021.151517 [doi] PST - ppublish SO - Int J Med Microbiol. 2021 Aug;311(6):151517. doi: 10.1016/j.ijmm.2021.151517. Epub 2021 Jun 30.