151. Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis
- Author
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Karina A. Pasquevich, Sandra Beer-Hammer, Guido H. Wabnitz, Stella E. Autenrieth, Kristin Hochweller, Manina Günter, Natalio Garbi, Doreen Drechsler, Günter J. Hämmerling, Philipp Warnke, Ana Novakovic, Cecilia S.M. Lucero Estrada, Ingo B. Autenrieth, and Yvonne Samstag
- Subjects
Adoptive cell transfer ,Phagocyte ,Neutrophils ,Cell Separation ,purl.org/becyt/ford/1 [https] ,Mice ,Homeostasis ,lcsh:QH301-705.5 ,Cells, Cultured ,Phagocytes ,Acquired immune system ,Adoptive Transfer ,Up-Regulation ,Bacterial Pathogens ,medicine.anatomical_structure ,Infectious Diseases ,Medicine ,Female ,CIENCIAS NATURALES Y EXACTAS ,Research Article ,lcsh:Immunologic diseases. Allergy ,PHAGOCITES ,Yersinia Infections ,Immune Cells ,Immunology ,Spleen ,Mice, Transgenic ,Biology ,DENDRITIC CELLS ,Microbiology ,Ciencias Biológicas ,Immune system ,Biología Celular, Microbiología ,Immunity ,Virology ,Genetics ,medicine ,Splenocyte ,Animals ,purl.org/becyt/ford/1.6 [https] ,Molecular Biology ,Yersinia enterocolitica ,Innate immune system ,Bacteria ,Dendritic Cells ,Immunity, Innate ,lcsh:Biology (General) ,Immune System ,Parasitology ,lcsh:RC581-607 - Abstract
Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection., Author Summary Dendritic cells (DCs) are professional antigen-presenting cells playing a crucial role in the initiation of T-cell responses to combat infection. DCs adapt their immune response according to the type of pathogen. For example, in response to intracellular bacteria, DCs produce IL-12, thereby initiating Th1 polarization, whereas in response to extracellular parasites or extracellular bacteria, DCs instruct Th2 or Th17 polarization, respectively. Nevertheless, their role in innate immunity is less well understood. To address this, we studied the role of DCs upon infection with the Gram-negative enteropathogenic bacteria Yersinia enterocolitica (Ye) and used a mouse model to deplete DCs. We found that DCs have an unexpected role during severe infection as depletion of these cells resulted in better outcome of infection as well as less bacterial load. We also found that DC depletion increased the number of phagocytes with improved anti-bacterial capacity in the spleen. Our study provides new insights into the role of DCs in innate immune response upon bacterial infection and points towards a complex interaction between DCs and phagocyte homeostasis. DC alteration during infection might also be an interesting target for immunotherapy in the future to guide the outcome of infection.
- Published
- 2011