Gene expression profiling in Helicobacter-induced MALT lymphoma with reference to antigen drive and protective immunization.
We have previously shown that long-term infection of BALB/c mice with gastric Helicobacter species results in the development of histopathological lesions that resemble those seen in patients diagnosed with gastric mucosa associated lymphoid tissue (MALT) lymphoma. This paper describes analysis of this disease at the molecular level through the use of microarray technology and immunohistochemical staining. We were able to monitor the genetic changes in the gastric mucosa characterized by distinct transcriptional signatures and correlate these with histological changes as the infection progressed from a chronic inflammatory infiltrate through to MALT lymphoma. This model system also enabled us to further dissect the role of antigen presentation and prophylactic immunization in the disease process. Antimicrobial therapy to eradicate the antigen correlated with significant reduction in pathology and major changes in the gene expression profile. Subsequent reintroduction of the antigen resulted in rapid tumor development which correlated with an increase in aggressively proliferating cells and changes in the cellular composition of the tumor. The response in vaccinated animals showed that the protected animals exhibited a strikingly different transcriptional profile compared to those of non-protected or control mice, indicating that the vaccination targeted the appropriate site leaving a long-lasting signature. The genes which were most significantly up-regulated included a number of adipocyte-specific factors, such as fat-cell specific cytokines and adipocyte surface markers. This study allowed for us to highlight the significance of antigen presentation in this disease and to hypothesis mechanisms associated with protective immunity.
O'Rourke
Jani L
JL
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia. j.orourke@unsw.edu.au
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000494:pharmacology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D007150:Immunohistochemistry; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism
D000890:Anti-Infective Agents; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D012333:RNA, Messenger