Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources

Bouabid Badaoui, Sem Genini*, Gert Sclep, Stephen C. Bishop, Dave Waddington, Marie-Helene Pinard-van der Laan, Christophe Klopp, Cedric Cabau, Hans-Martin Seyfert, Wolfram Petzl, Kirsty Jensen, Elizabeth J. Glass, Astrid de Greeff, Hilde E. Smith, Mari A. Smits, Ingrid Olsaker, Guro M. Boman, Giuliano Pisoni, Paolo Moroni, Bianca CastiglioniPaola Cremonesi, Marcello Del Corvo, Eliane Foulon, Gilles Foucras, Rachel Rupp, Elisabetta Giuffra

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged in vivo with S. aureus, E. coli, and S. uberis, samples from goats challenged in vivo with S. aureus, as well as cattle macrophages and ovine dendritic cells infected in vitro with S. aureus. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific.

Results: Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e. g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including XBP1 and SREBF1.

The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of E. coli and S. aureus infections in cattle in vivo revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that E. coli caused a stronger host response.

Conclusions: This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources.

Original languageEnglish
Article numberARTN 225
Pages (from-to)17
Number of pages17
JournalBMC Genomics
Issue number225
Publication statusPublished - 11 May 2011

Keywords / Materials (for Non-textual outputs)

  • Meta-analysis microarray analysis mastitis infection lipid metabolism immune response acute-phase response endoplasmic-reticulum stress data integration methodology unfolded protein response cytokine interferon-gamma negative-energy balance open-access-publication multiple cancer types gene-expression escherichia-coli


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