Abstract
BackgroundWe infected freshly isolated human peripheral monocytes with live bacteria of three clinically important gram-positive bacterial species, Staphylococcus aureus, Streptococcus pneumoniae and Listeria monocytogenes and studied the ensuing early transcriptional response using expression microarrays. Thus the observed response was unbiased by signals originating from other helper and effector cells of the host and was not limited to induction by solitary bacterial constituents.ResultsActivation of monocytes was demonstrated by the upregulation of chemokine rather than interleukin genes except for the prominent expression of interleukin 23, marking it as the early lead cytokine. This activation was accompanied by cytoskeleton rearrangement signals and a general anti-oxidative stress and anti-apoptotic reaction. Remarkably, the expression profiles also provide evidence that monocytes participate in the regulation of angiogenesis and endothelial function in response to these pathogens.ConclusionRegardless of the invasion properties and survival mechanisms of the pathogens used, we found that the early response comprised of a consistent and common response. The common response was hallmarked by the upregulation of interleukin 23, a rather unexpected finding regarding Listeria infection, as this cytokine has been linked primarily to the control of extracellular bacterial dissemination.
Highlights
We infected freshly isolated human peripheral monocytes with live bacteria of three clinically important gram-positive bacterial species, Staphylococcus aureus, Streptococcus pneumoniae and Listeria monocytogenes and studied the ensuing early transcriptional response using expression microarrays
Germany Full list of author information is available at the end of the article induced immune activation, we examined the total transcriptional response of isolated peripheral human CD14+/CD11b+ monocytes, infected with the viable bacterial pathogens: Listeria monocytogenes, Staphylococcus aureus and Streptococcus pneumoniae
We employed DNA expression microarrays to study the early transcriptional response of naïve human peripheral monocytes infected with a set of three important grampositive bacterial pathogens: Staphylococcus aureus, Streptococcus pneumoniae and Listeria monocytogenes
Summary
We infected freshly isolated human peripheral monocytes with live bacteria of three clinically important gram-positive bacterial species, Staphylococcus aureus, Streptococcus pneumoniae and Listeria monocytogenes and studied the ensuing early transcriptional response using expression microarrays. A number of recent publications have investigated the transcriptional response to killed or inactive gram-positive pathogens, or the contribution of gram-positive cell wall constituents such as peptidoglycan (PepG), lipopeptide (LP) and lipoteichoic acid (LTA) to the triggering of specific host defense responses [6,7,8,9,10] Though such studies are crucial for identifying stimulus specific effects, they are unable to account for the immunomodulatory effects of live bacteria, which frequently employ multiple survival strategies in parallel. We designed and established a protocol enabling the detection of pathological changes early in the onset of infections with gram positive pathogens, before usual clinical parameters are upregulated, in an accessible cellular sample material For these purposes, we focused our experimental analysis of naïve monocytes, which are easier to work with in ex vivo conditions than granulocytes, even though they are represented in much lower numbers in vivo than the latter. This program is characterized by the upregulation of a key cytokine - interleukin 23 (IL23)
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