Change search
ReferencesLink to record
Permanent link

Direct link
Transcriptional profiling of the peripheral blood response during tularemia.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
Universitetssjukhuset i Örebro.
Universitetssjukhuset i Örebro.
Show others and affiliations
2006 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 7, no 6, 503-513 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 7, no 6, 503-513 p.
National Category
Microbiology in the medical area Microbiology in the medical area
URN: urn:nbn:se:umu:diva-7831DOI: 10.1038/sj.gene.6364321PubMedID: 16826236OAI: diva2:147502
Available from: 2008-07-10 Created: 2008-07-10 Last updated: 2012-09-07
In thesis
1. A microarray analysis of the host response to infection with Francisella tularensis
Open this publication in new window or tab >>A microarray analysis of the host response to infection with Francisella tularensis
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Francisella tularensis is a gram-negative bacterium that is the cause of the serious and sometimes fatal disease, tularemia, in a wide range of animal species and in humans. The response of cells of the mouse macrophage cell line J774 to infection with Francisella tularensis LVS was analyzed by means of a DNA microarray. It was observed that the infection conferred an oxidative stress upon the target cells and many of the host defense mechanisms appeared to be intended to counteract this stress. The infection was characterized by a very modest inflammatory response.

Tularemia caused by inhalation of F. tularensis subspecies tularensis is one of the most aggressive infectious diseases known. We used the mouse model to examine in detail the host immune response in the lung. After an aerosol challenge all mice developed clinical signs of severe disease, showed weight loss by day four of infection, and died the next day. Gene transcriptional changes in the mouse lung samples were examined on day one, two, and four of infection. Genes preferentially involved in host immune responses were activated extensively on day four but on day one and two, only marginally or not at all. Several genes upregulated on day four are known to depend on IFN-gamma or TNF-alpha for their regulation. In keeping with this finding, TNF-alpha and IFN-gamma levels were found to be increased significantly in bronchoalveolar lavage on day four.

We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays. Samples were obtained from seven individuals at five occasions during two weeks after the first hospital visit and convalescent samples three months later. In total 265 genes were differentially expressed. The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an IFN-gamma-induced response and also a pro-apoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia.

Recently, a large number of methods for the analysis of microarray data have been proposed but there are few comparisons of their relative performances. We undertook a study to evaluate established and novel methods for filtration, background adjustment, scanning, and censoring. For all analyses, the sensitivities at low false positive rates were observed together with a bias measurement. In general, there was a trade off between the analyses ability to identify differentially expressed genes and their ability to obtain unbiased estimators of the desired ratios. A commonly used standard analysis using background adjustment performed poorly. Interestingly, the constrained model combining data from several scans resulted in high sensitivities. For experiments where only low false discovery rates are acceptable, the use of the constrained model or the novel partial filtration method are likely to perform better than some commonly used standard analyses.

Place, publisher, year, edition, pages
Umeå: Klinisk mikrobiologi, 2006. 59 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1029
Francisella tularensis, tularemia, host response, gene expression, microarray
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-792 (URN)91-7264-081-2 (ISBN)
Public defence
2006-05-31, E04, 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Available from: 2006-05-10 Created: 2006-05-10 Last updated: 2009-09-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ryden, Patrik
By organisation
Clinical Bacteriology
In the same journal
Genes and Immunity
Microbiology in the medical areaMicrobiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 61 hits
ReferencesLink to record
Permanent link

Direct link