Yersinia enterocolitica impairs dendritic cell development

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

Rothenfels

Simposio; Symposium Infektion und Immunabwehr; 2011

Deutsche Gesellschaft für Immunologie (Sociedad Alemana de Inmunología)

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. This decrease was partially TLR4-dependent and not due to increased cell death. MDPs and CDPs did not migrate out from BM before differentiation into pre-cDCs, as they were not present in blood or spleens of infected mice. Furthermore, levels of pre-cDCs in spleens were reduced during Ye infection. Moreover, BM DC precursors from infected mice proliferated stronger and developed into all cDC subpopulations when transferred to non-infected mice, indicating that their functionality is intact. All in all, our results indicate that Ye infection causes a partial depletion of cDC precursors in BM and spleen. Further experiments are needed to elucidate if this is the source or an outcome of the Ye induced cDCs-depletion in spleens