Differential Gene Expression in Gram-negative and Gram-positive Sepsis

Abstract

Sepsis is the most common cause of death in patients in the intensive care unit. Genome-wide gene expression analysis can provide insights into the molecular alterations of sepsis. Total mRNA was extracted from the livers of 6 uninfected control mice and 60 septic mice after infusion of either live Escherichia coli or Staphylococcus aureus. Using a murine complementary DNA microarray system, changes in gene expression were monitored at six time points (uninfected, 2, 8, 24, 48, and 72 hours). Overall, 4.8% of 6,144 assessed genes were differentially regulated with a greater than twofold change across all time points. Most of the genes with altered expression were commonly present in gram-negative and gram-positive sepsis, but the expression levels of 17 genes were different between both types of sepsis at particular time points after infection. The microarray results support the hypothesis that both gram-positive and gram-negative sepsis share a final common pathway involved in the pathogenesis of sepsis, but certain genes are differentially expressed under distinct regulation. These results may provide insights into the pathogenesis of sepsis and may also help identify some altered genes that can serve as new targets for diagnostic tools and therapeutic strategies.

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

“…29 Our data also revealed that host immune response assessed by using gene expression patterns may be different in children infected with Gram-positive versus Gram-negative bacteria. This is in agreement with studies by Ramilo et al, 18 Feezor et al, 39 and Yu et al 40 In contrast, Tang et al 41 did not find significant differences in critically ill adults. Nevertheless, these data need to be interpreted with caution because of the limited number of children with Gram-negative sepsis.…”

Monitoring Immune Dysfunctions in the Septic Patient: A New Skin for the Old Ceremony

“…Initially, numerous studies examined the cellular response to different microbial pathogens or pathogen-associated molecular patterns (PAMPs) in vitro. Changes in gene expression after stimulation have been experimentally studied in human circulating leukocytes (161), DCs (162,163), and differentiated human macrophages (164) and in several animal models (165)(166)(167). Recent studies took advantage of this approach to assess whether it could successfully be applied to the differentiation between sterile systemic inflammation and sepsis in ICU patients (168)(169)(170).…”

Transcriptional profiling of the peripheral blood response during tularemia

“…In a murine model of sepsis, 4.8% of the investigated genes were differentially regulated but only 0.3% of these discriminated between Gram-negative and Gram-positive sepsis. 2 In a macaque model of smallpox, generalized responses representing IFN-regulation genes, cell proliferation genes and immunoglobulin genes were observed. 1 However, also a lack of proinflammatory response involving TNF-a-and NF-kBdependent genes was noted, suggesting that smallpox may abrogate this response.…”

“…1 In a murine model of sepsis, the transcriptional response of peripheral blood cells (PBC) was undertaken. 2 Some 5% of assessed genes were differentially regulated and most of the genes were present in both Gram-negative and Gram-positive sepsis. Thus, the implementation of the large-scale microarray technique is a powerful tool for elucidating the specific host adaptation to infection.…”