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| Home > Publications database > Systemic bacterial infections affect dendritic cell development and function. |
| Journal Article | DKFZ-2021-01540 |
; ; ;
2021
Elsevier
München
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Please use a persistent id in citations: doi:10.1016/j.ijmm.2021.151517
Abstract: 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-γ 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.
Keyword(s): Dendritic cells ; Development ; Escherichia coli ; Infection ; Innate immune defense ; Monocytes ; Staphylococcus aureus ; TLR
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