The innate immune system favors emergency monopoiesis at the expense of DC differentiation to promote control of bacterial pathogens

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

Kos

Congreso; 10th International Conference on Innate Immunity; 2013

Aegean Conferences

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 employed a previously described mouse model of systemic bacterial infection to analyze in vivo the impact of different bacteria on DC development. We found that exposure to bacterial infection reduced the numbers of bone marrow hematopoietic progenitors of the monocyte and DC lineages in a TLR4-dependent manner, irrespectively of the individual pathogen. This reduction occurred concomitant to increased numbers of monocyte progenitors in the bone marrow and monocytes in the spleen during infection, whereas the number of newly generated DCs is reduced. Mechanistically bacterial infection led to increased MafB expression in MDPs, whereas the expression of PU.1 was unaltered, indicating a biased differentiation of myeloid progenitors into monocytes. Our study support the notion, that systemic bacterial infection leads to a general attrition of myeloid progenitors in the bone marrow and cDCs in the periphery, which can be compensated by emergency monopoiesis not only to sustain but even increase the numbers of innate immune monocytes to promote pathogen control.