dendritic cell cross-priming is essential for immune responses to listeria monocytogenes树突细胞cross-priming单核细胞增多性李斯特氏菌对免疫反应至关重要.pdfVIP

Dendritic Cell Cross-Priming Is Essential for Immune Responses to Listeria monocytogenes Anna T. Reinicke, Kyla D. Omilusik, Genc Basha, Wilfred A. Jefferies* The Biomedical Research Centre, Michael Smith Laboratories, Departments of Medical Genetics, Microbiology and Immunology, and Zoology, The Unive rsity of British Columbia, Vancouver, British Columbia, Canada Abstract Cross-presentation is now recognized as a major mechanism for initiating CD8 T cell responses to virus and tumor antigens in vivo. It provides an elegant mechanism that allows relatively few Dendritic cells (DCs) to initiate primary immune responses while avoiding the consumptive nature of pathogenic infection. CD8 T cells play a major role in anti-bacterial immune responses; however, the contribution of cross-presentation for priming CD8 T cell responses to bacteria, in vivo, is not well established. Listeria monocytogenes (Listeria) is the causative agent of Listeriosis, an opportunistic food-borne bacterial infection that poses a significant public health risk. Here, we employ a transgenic mouse model in which cross- presentation is uniquely inactivated, to investigate cross-priming during primary Listeria infection. We show that cross- priming deficient mice are severely compromised in their ability to generate antigen-specific T cells to stimulate MHC I- restricted CTL responses following Listeria infection. The defect in generation of Listeria-elicited CD8 T cell responses is also apparent in vitro. However, in this setting, the endogenous route of processing Listeria-derived antigens is predominant. This reveals a new experimental dichotomy whereby functional sampling of Listeria-derived antigens in vivo but not in vitro is dependent