Transcriptional responses of murine macrophages to infection with Yersinia enterocolitica.
Transcriptional responses of J774 murine macrophage-like cells to infection with Yersinia enterocolitica were evaluated with oligonucleotide microarrays interrogating 12 488 genes and expressed sequence tags. Virulence plasmid (pYV)-cured yersiniae induce a transcriptional programme resembling a general inflammatory response. pYV-carrying yersiniae translocating the Yersinia outer proteins (Yops) impact on this transcriptional programme in two ways: first, by suppressing this inflammatory response and, secondly, by inducing sustained expression of a distinct set of genes with known silencing functions. These tranquilizing patterns of gene expression could be confirmed by real-time reverse transcription polymerase chain reaction, are stable upon reduction in bacterial load and could also be reproduced in BALB/c-derived bone marrow macrophages. Prestimulation of macrophages with interferon (IFN)-gamma, but not with interleukin (IL)-4, induces partial resistance against pYV-mediated transcriptional tranquilization. The first effect, suppression of the inflammatory programme, is mediated by YopP, whereas no YopH- or YopM-regulated genes could be identified under our stringent statistical criteria. The bacterial protein responsible for the second effect, induction of silencing genes, remains elusive. We suggest that Yersinia enterocolitica might use two independent mechanisms to inhibit macrophage inflammatory responses at the transcriptional level.
Hoffmann
Reinhard
R
Max-von-Pettenkofer-Institut, Bacteriology Department, Pettenkoferstrasse 9A, 80336 Munich, Germany. r_hoffmann@m3401.mpl.med.uni-muenchen.de
van Erp
Katrin
K
Trülzsch
Konrad
K
Heesemann
Jürgen
J
D018829:Adhesins, Bacterial / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005798:Genes, Bacterial; D007041:Hypoxanthine Phosphoribosyltransferase / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014774:Virulence; D015008:Yersinia enterocolitica / Q000472:pathogenicity*; D020743:rhoB GTP-Binding Protein / Q000032:analysis
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D007041:Hypoxanthine Phosphoribosyltransferase; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D020743:rhoB GTP-Binding Protein