Transcriptional reprograming of dendritic cell committed hematopoietic progenitors by bacterial infection

KARINA A. PASQUEVICH; MANINA GÜNTER; MATTHIAS GRAUER; TILO BIEDERMANN; SANDRA BEER-HAMMER; HANS-JÖRG BÜHRING; HANS-GEORG RAMMENSEE; INGO B. AUTENRIETH; CLAUDIA LENGERKE; STELLA E. AUTENRIETH

Paris

Congreso; Annual Meeting ?Diversity and plasticity of DCs?; 2012

CLUB FRANCOPHONE DES CELLULES DENDRITIQUES - Istitut Pasteur

Dendritic cells (DCs) are critical in host defense against infection, bridging the innate and adaptive immune systems. How pathogens influence DC commitment remains still elusive. Here we report that DC committed bone marrow progenitor cells are reduced upon systemic infection with Gram-positive or Gram-negative bacterial pathogens in a TLR-dependent manner. This reduction is not due to cell death or migration of DC progenitors from the BM before differentiation, but rather to a biased differentiation of monocyte DC progenitors (MDPs) into monocytes by up regulation of MafB. Interestingly, live but not dead bacteria actively inhibit the differentiation capacity of common DC progenitors (CDPs) into DCs possibly by reprogramming them to differentiate into inflammatory monocyte-like cells.