Activation of the transcription factor interferon regulatory factor-3 (IRF-3) is an essential event in the innate immune response to viral infection. To understand the contribution of IRF-3 to host defense, we used a systems biology approach to analyze global gene expression dependent on IRF-3. Comparison of expression profiles in cells from IRF-3 knockout animals or wild-type siblings following viral infection revealed three sets of induced genes, those that are strictly dependent on IRF-3, augmented with IRF-3, or not responsive to IRF-3. Products of identified IRF-3 target genes are involved in innate or acquired immunity, or in the regulation of cell cycle, apoptosis and proliferation. These results reveal the global effects of one transcription factor in the immune response and provide information to evaluate the integrated response to viral infection.

The human pathogen Neisseria gonorrhoeae produces an array of diseases ranging from urethritis to disseminated gonococcal infections. Early events in the establishment of infection involve interactions between N. gonorrhoeae and the mucosal epithelium, which leads to the local release of inflammatory mediators. Because of this, it is important to identify the bacterial virulence factors and host cell components that contribute to inflammation. Using a series of column chromatography steps, we purified a lipoprotein from N. gonorrhoeae strain F62 called Lip. This outer membrane antigen expresses a conserved epitope known as H.8, which is common to all pathogenic Neisseria species. We found the purified preparation of Lip to be a potent inflammatory mediator capable of inducing the release of the chemokine interleukin (

High body mass index (BMI) is negatively associated with semen quality. In addition, the composition of fatty acids of spermatozoa has been shown to be important for their function. The aim of the study was to examine the association between BMI and the composition of spermatozoa fatty acids in men spanning a broad BMI range. We also analysed the relation between fatty acid composition of spermatozoa and semen characteristics, and the relationship between serum fatty acids and spermatozoa fatty acids. One hundred forty-four men with unknown fertility status were recruited from the general population, from couples with identified female infertility and from morbid obesity centres. Standard semen analysis (WHO) and sperm DNA integrity (DFI) analysis were performed. Fatty acid compositions were assessed by gas chromatography. When adjusted for possible confounders, BMI was negatively associated with levels of sperm docosahexaenoic acid (DHA) (p < 0.001) and palmitic acid (p < 0.001). The amount of sperm DHA correlated positively with total sperm count (r = 0.482), sperm concentration (r = 0.469), sperm vitality (r = 0.354), progressive sperm motility (r = 0.431) and normal sperm morphology (r = 0.265). A negative association was seen between DHA levels and DNA fragmentation index (r = -0.247). Levels of spermatozoa palmitic acid correlated positively with total sperm count (r = 0.227), while levels of linoleic acid correlated negatively (r = -0.254). When adjusted for possible confounders, only the levels of arachidonic acid showed positive correlation between spermatozoa and serum phospholipids (r = 0.262). Changes in the fatty acid composition of spermatozoa could be one of the mechanisms underlying the negative association between BMI and semen quality. The relationship between fatty acids of spermatozoa and serum phospholipids was minor, which indicates that BMI affects fatty acid composition of spermatozoa through regulation of fatty acid metabolism in the testis. The role of dietary intake of fatty acids on the spermatozoa fatty acid composition remains to be elucidated.

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