Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica.
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-kappaB 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.
van Erp
Katrin
K
Department of Bacteriology, Max von Pettenkofer-Institut, Munich, Germany.
Dach
Kristina
K
Koch
Isabel
I
Heesemann
Jürgen
J
Hoffmann
Reinhard
R
D000818:Animals; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D013045:Species Specificity; D013997:Time Factors; D014158:Transcription, Genetic; D015009:Yersinia Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000472:pathogenicity*
D007371:Interferon-gamma