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.
Highlights
Innate immunity as well as adaptive immunity is involved in the response of the host towards pathogens [1,2,3]
We have recently shown that the Gram-negative bacterium Yersinia enterocolitica (Ye) affects the homeostasis of the CD4+ DCs and, to a lesser extent, the CD8a+ DC population in the spleen by Dendritic cells (DCs) are professional antigen-presenting cells playing a crucial role in the initiation of T-cell responses to combat infection
We found that DC depletion per se increased the number of phagocytes and enhanced their anti-bacterial host defense in the spleen leading to increased survival of the mice upon Ye infection
Summary
Innate immunity as well as adaptive immunity is involved in the response of the host towards pathogens [1,2,3]. Dendritic cells (DCs) are professional antigen presenting cells playing a central role in immune response by linking the innate and adaptive immunity [4,5,6]. Upon stimulation by TLR ligands, DCs mature and migrate from the site of infection to secondary lymphoid organs to induce pathogen-specific T-cell responses. Previous studies showed that the induction of sepsis in mice resulted in a profound loss of CD11c+ DCs from spleen and lymph nodes [8,9]. The administration of LPS or Escherichia coli in mice causes a pronounced reduction in DC numbers in the spleen induced by apoptosis [10,11]. Scumpia et al showed that DCs were essential in the immune response to sepsis and suggested that strategies to maintain DC numbers or function may improve the outcome during polymicrobial sepsis [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
