Yersinia enterocolitica impairs dendritic cell development

KARINA A. PASQUEVICH; TANJA R. LINZER; MANINA GÜNTER; INGO B. AUTENRIETH; STELLA E. AUTENRIETH

Bruselas

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

European Macrophage & Dendritic Cell Society

Yersinia enterocolitica (Ye) is a Gram-negative predominantly extracellularly located bacterium that causes food borne acute or chronic gastrointestinal and systemic diseases. In mice, Ye infection reduces the number of splenic CD8α+ and CD4+ conventional dendritic cellls (cDCs) by 50 and 90%, respectively. The decreased number of cDCs is dependent on TLR4 and TRIF signalling and the result of both faster turn over and suppressed de novo cDC generation. To address the mechanisms of the suppressed de novo cDCs generation, we analyzed whether Ye infection causes an inhibition of the development of DC-precursors. We analyzed monocyte and DC precursors (MDPs), common DC progenitors (CDPs) and direct precursors for cDCs (pre-cDCs) in bone marrow (BM), blood and spleens of infected mice. Our results indicated that Ye infection led to a decreased number of all cDCs-precursors analyzed in BM and spleen. This decrease was partially TLR4-dependent and not due to increased cell death. MDPs and CDPs did not migrate out from BM before differentiation. Moreover, BM DC precursors from infected mice proliferated stronger and at the same time there was an increase in BM-monoblasts and pro-monocytes, blood-circulating monocytes and splenic monocytes. All in all, our results indicate that Ye infection causes a partial depletion of cDC precursors in BM and spleen, but an increment in other myeloid cells that share same precursors, like monocytes. Further experiments are needed to elucidate if Ye induced cDCs-precursors depletion is due to a shift into the production of monocytes by myeloid precursors.