SEP-4: A NOVEL ROLE OF CHEMOKINE RECEPTOR XXXX IN THE DEVELOPMENT OF IMMUNOSUPPRESSION DURING POLYMICROBIAL SEPSIS: IMPACT ON DENDRITIC CELL DIFFERENTIATION.

@entity295 @entity776 @entity19 @entity9843 @entity1618 @entity1961 @entity9019 @entity72193
INTRODUCTION: @entity295 leads to an enhanced susceptibility to secondary infections due to development of immunosuppression. We have previously shown that dysfunctional dendritic cells (DCs) that characteristically secrete @entity1618 differentiate from bone marrow (BM) during polymicrobial @entity295 and contribute to immunosuppression. METHODS: We investigated the origin of the altered DC differentiation in the BM during polymicrobial @entity295 induced by cecal ligation and puncture (CLP) in @entity19 . RESULTS: Analysis of the cellular composition of the BM revealed the appearance of @entity776 ( @entity1961 +DC) in the BM 18 to 36h after CLP. Depletion of @entity1961 +DC from BM after CLP prevented the differentiation of dysfunctional DC. The chemokine receptor @entity9843 is relevant for the retention and attraction of leukocytes in/to the BM. @entity19 with a DC-specific knockout of @entity9843 ( @entity72193 ko) were generated with the Cre-loxP system. After CLP, @entity1961 +DCs did not appear in the BM of @entity72193 ko @entity19 and of @entity19 treated with the @entity9843 inhibitor @entity9019 but instead circulated in the blood. Adoptive transfer of peritoneal exudate cells from @entity72193 ko @entity19 into the peritoneal cavity of wildtype @entity19 reduced the appearance of @entity1961 +DC in the BM and prevented the differentiation of @entity1618 secreting DCs. Tracking experiments showed that @entity1961 +DCs that appeared in the BM after CLP did not originate from the peritoneal cavity. CONCLUSION: So far, unidentified cells in the peritoneal cavity are challenged in a @entity9843 -dependent manner after CLP and indirectly induce the migration of @entity1961 +DCs from blood into the BM where they favor the differentiation of dysfunctional DCs.
