Impairment of dendritic cell de novo generation by Yersinia enterocolitica infection

KARINA A. PASQUEVICH; MANINA GÜNTER; STELLA E. AUTENRIETH

Rothenfels

Simposio; Symposium ?Infektion und Immunabwehr?; 2012

Deutsche Gesellschaft für Immunologie (Sociedad Alemana de Inmunología)

Yersinia enterocolitica (Ye) is a Gram-negative predominantly extracellular located bacterium that causes food borne acute or chronic gastrointestinal and systemic diseases. Ye systemic infection in mice induces a reduction of splenic conventional dendritic cells (cDCs). 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. The aim of this work was to address the mechanisms of the suppressed de novo cDCs generation upon Ye infection. Therefore we analysed whether Ye infection interferes with DC-precursors in bone marrow (BM), blood and spleen. We analyzed monocyte and DC precursors (MDPs), common DC progenitors (CDPs) and direct precursors for cDCs (pre-cDCs). Our results indicated that Ye infection led to a decreased number of all cDCs-precursors analyzed in BM and spleen in a TLR4 dependent maner. MDPs and CDPs did not migrate out from BM before differentiation into pre-cDCs upon Ye infection, as they were not present in blood or spleen of infected mice. The reduction of MDPs and CDPs was not due to increased cell death, quite the opposite these cells proliferated stronger after Ye infection. Furthermore, Ye infection induced 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 increase 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.