Depletion of dendritic cells enhances innate anti-bacterial host defense through modulation of phagocyte homeostasis

STELLA E. AUTENRIETH; PHILIPP WARNKE; GUIDO H. WABNITZ; CECILIA LUCERO ESTRADA; KARINA A. PASQUEVICH; DOREEN DRECHSLER; MANINA GÜNTER; KRISTIN HOCHWELLER; ANA NOVAKOVIC; SANDRA BEER-HAMMER; YVONNE SAMSTAG; GÜNTER J. HÄMMERLING; NATALIO GARBI; INGO B. AUTENRIETH

Bruselas

Congreso; Annual EMDS Meting. Clinical and Fundamental Aspects of Monocyte, Macrophage and DC Plasticity; 2011

European Macrophage & Dendritic Cell Society

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of innate and adaptive immune responses. Here, we have analyzed the role of DCs and their impact on bacterial clearance in an experimental model of the extracellular bacterium Yersinia enterocolitica (Ye). We used CD11c-diphteria toxin (DT) mice to deplete DCs during an infection with Ye. DC depletion significantly increased the survival after Ye infection. Interestingly, throughout the infection the bacterial load in the spleen of DC depleted mice was significantly lower than that of wild type control mice. This was accompanied by an increase in the serum chemokine levels of CXCL1, G-CSF, IL-1
, and MCP-1 (CCL3) upon DC depletion and an increase in the frequency and numbers of phagocytes, namely PMNs and monocytes. Splenocytes from DC depleted mice exhibited increased bacterial killing capacity compared to splenocytes from wild type control mice. Ye colocalized more frequently with the phagocytes in DC depleted mice compared to wild type mice. DC depletion improved phagocytic activity, production of reactive oxygen species and Ye killing capacity by PMNs. Adoptive transfer of Gr-1+ cells from DC depleted mice into wild type mice prior to Ye infection reduced the bacterial load to the level of Ye infected DC-depleted mice, demonstrating that the increased number of effective phagocytes resulting from DC depletion accounts for the initial differences in the bacterial load. Beyong bacterial infection, our data indicate that DCs regulate the homeostasis of PMNs and monocytes into the spleen by a yet unknown mechanism.