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Physiol. Genomics 25: 75-84, 2006. First published December 13, 2005; doi:10.1152/physiolgenomics.00188.2005
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Received 27 July 2005; accepted in final form 6 December 2005.
Physiological Genomics 25:75-84 (2006)
American Physiological Society © 2006 American Physiological Society

Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica

Katrin van Erp, Kristina Dach, Isabel Koch, Jürgen Heesemann and Reinhard Hoffmann

Max von Pettenkofer-Institut, Department of Bacteriology, Munich, Germany

The outcome of a host-pathogen encounter is determined by virulence factors of the pathogen and defense factors of the host. We characterized the impact of host factors [resistant (C57BL/6) or susceptible (BALB/c) genetic background and exposure to interferon (IFN)-{gamma}] on transcriptional responses of bone marrow-derived macrophages (BMDM) to infection with Yersinia enterocolitica. IFN-{gamma} treatment more profoundly altered the transcriptome of BMDM than did bacterial infection or genetic background. In BALB/c BMDM, 1,161 genes were differentially expressed in response to Yersinia infection with or without IFN-{gamma} prestimulation. Fourteen genes (1.2%) could only be induced by BALB/c BMDM in response to Yersinia infection after IFN-{gamma} pretreatment. These genes inhibit apoptosis, activate NF-{kappa}B and Erk signaling, are chemotactic to neutrophils, and are involved in cytoskeletal reorganization, hence possibly in phagocytosis. Ten of these genes possess a common module of binding sites for Hox, Pou, and Creb transcription factors in 2 kb of upstream genomic sequence, suggesting a possible novel role of these transcription factors in regulation of immune responses. Fifty-two of one thousand fifty differentially expressed genes (4.9%) were induced more strongly by C57BL/6 BMDM in response to Yersinia infection than BALB/c BMDM. These genes activate NK cells, have antibacterial properties, or are involved in sensing chemokines and lipopolysaccharide (LPS). These data show that host resistance factors modulate a surprisingly small, but identifiable and functionally significant, portion of the macrophage transcriptome in response to Yersinia infection.

bacterial infection; host response; BALB/c; C57BL/6




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Proc. Natl. Acad. Sci. USAHome page
L. R. Hoffman and S. I. Miller
The systems biology of infection in animal models bears fruit
PNAS, June 20, 2006; 103(25): 9377 - 9378.
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