Cytokine induction by purified lipoteichoic acids from various bacterial species - Role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-γ release

Hermann, Corinna; Spreitzer, Ingo; Schröder, Nicolas W.J.; Morath, Siegfried; Lehner, Martin D.; Fischer, Werner; Schütt, Christine; Schumann, Ralf R.; Hartung, Thomas

doi:10.1002/1521-4141(200202)32:2<541::aid-immu541>3.0.co;2-p

Cited by 124 publications

(93 citation statements)

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“…This is in accordance with the reports by Schrö-der et al (32) showing a CD14 dependence of LTA-induced activation of human monocytes by inhibition with anti-CD14 antibodies and Lotz et al (52), who showed a role for CD14 in the activation of neutrophil granulocytes by LTA. In contrast, Hermann et al (36) described that cytokine production in human whole blood was inhibited by the addition of sCD14, and sCD14 was not able to confer a response to LTA on endothelial cells. This contradiction might reflect different roles of soluble and membrane-bound CD14 in cell activation by LTA.…”

Section: Discussionmentioning

confidence: 94%

“…Interaction of LTA with serum proteins has been reported previously, but the data published on the requirement of soluble LBP are conflicting. Thus, it has been reported that recombinant human LBP enhances the response of human monocytes to LTA preparations (32), whereas in another publication no influence of recombinant murine LBP on the cell activation of human monocytes could be observed (35,36). The discrepancy of these observations might be due to species-specific effects or differences in the test systems employed.…”

Section: Discussionmentioning

confidence: 98%

“…However, it is now generally accepted that LTA activates immune responses via a TLR2/TLR6 heterodimer (31,32). There are, nevertheless, still conflicting reports on the requirement of CD14 (33,34) and LBP in LTA-mediated cellular responses, ranging from enhancing to no effects of LBP on cell activation by LTA (32,35,36). In the current study, we investigated the role of serum and LBP in cell activation by LTA.…”

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confidence: 99%

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Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

et al. 2006

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Lipoteichoic acid (LTA) represents immunostimulatory molecules expressed by Gram-positive bacteria. They activate the innate immune system via Toll-like receptors. We have investigated the role of serum proteins in activation of human macrophages by LTA from Staphylococcus aureus and found it to be strongly attenuated by serum. In contrast, the same cells showed a sensitive response to LTA and a significantly enhanced production of tumor necrosis factor ␣ under serum-free conditions. We show that LTA interacts with the serum protein lipopolysaccharide-binding protein (LBP) and inhibits the integration of LBP into phospholipid membranes, indicating the formation of complexes of LTA and soluble LBP. The addition of recombinant human LBP to serum-free medium inhibited the production of tumor necrosis factor ␣ and interleukins 6 and 8 after stimulation of human macrophages with LTA in a dose-dependent manner. Using anti-LBP antibodies, this inhibitory effect could be attributed to soluble LBP, whereas LBP in its recently described transmembrane configuration did not modulate cell activation. Also, using primary alveolar macrophages from rats, we show a sensitive cytokine response to LTA under serum-free culture conditions that was strongly attenuated in the presence of serum. In summary, our data suggest that innate immune recognition of LTA is organ-specific with negative regulation by LBP in serum-containing compartments and sensitive recognition in serum-free compartments like the lung.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

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confidence: 99%

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Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

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“…It may be related to whether the bacteria is gram-negative or -positive. 61 Alternatively, anthrax lethal toxin (lethal factor ϩ PA) inhibits dendritic cell maturation 62 and kills macrophages, 63 which would selectively compromise immune responsiveness and favor bacterial survival.…”

Section: Discussionmentioning

confidence: 99%

Sepsis and Pathophysiology of Anthrax in a Nonhuman Primate Model

Stearns-Kurosawa

Lupu

Taylor

et al. 2006

The American Journal of Pathology

103

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Studies that define natural responses to bacterial sepsis assumed new relevance after the lethal bioterrorist attacks with Bacillus anthracis (anthrax), a spore-forming, toxigenic gram-positive bacillus. Considerable effort has focused on identifying adjunctive therapeutics and vaccines to prevent future deaths, but translation of promising compounds into the clinical setting necessitates an animal model that recapitulates responses observed in humans. Here we describe a nonhuman primate (Papio c. cynocephalus) model of B. anthracis infection using infusion of toxigenic B. anthracis Sterne 34F2 bacteria (5 ؋ 10 5 to 6.5 ؋ 10 9 CFU/kg). Similar to that seen in human patients, we observed changes in vascular permeability, disseminated intravascular coagulation, and systemic inflammation. The lung was a primary target organ with serosanguinous pleural effusions, intra-alveolar edema, and hemorrhagic lesions. This animal model reveals that a fatal outcome is dominated by the host septic response, thereby providing important insights into approaches for treatment and prevention of anthrax in humans. (Am J Pathol

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“…For peptidoglycan, these immune stimulatory effects are controversially discussed and might be due to LTA contaminations [29,30]. Therefore, we used only LTA, which induces a cytokine profile different from LPS [31,32] and signals via TLR2 [33].…”

Section: Introductionmentioning

confidence: 99%

Endogenous cortisol determines the circadian rhythm of lipopolysaccharide‐ but not lipoteichoic acid‐inducible cytokine release

et al. 2006

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To investigate the circadian rhythm of inducible cytokine release and a potential pacemaker role of endogenous cortisol, cortisol levels as well as cytokine release from ex vivo LPS-stimulated blood were assessed at 4-h intervals over 24 h in 11 volunteers. We found a significant diurnal variation for IFN-c and IL-8, and a tendency for TNF, all inversely correlated to the serum cortisol levels, but no evidence for such a rhythm for IL-1b and IL-6. In vitro IC 50 values for cytokine inhibition by hydrocortisone (HC) corresponded to the observed rank order for circadian rhythmicity. mRNA analyses revealed that this was due to a reduction of gene transcription. These effects of HC were significantly reversed by the glucocorticoid receptor antagonist RU486. Supplementation of HC in vivo to maintain morning cortisol levels throughout the day blunted the circadian rhythm of ex vivo LPS-induced cytokines. Surprisingly, no significant diurnal variation for any investigated cytokine was found in the same volunteer group upon stimulation with lipoteichoic acid (LTA), the gram-positive counterpart to LPS. Furthermore, 10-50-fold higher HC concentrations as compared to LPS were required to block LTA-induced cytokine release. LTA, in contrast to LPS, failed to activate Jun kinase, a reported target for HC action.

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Cytokine induction by purified lipoteichoic acids from various bacterial species - Role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-γ release

Cited by 124 publications

References 41 publications

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

Cell Activation of Human Macrophages by Lipoteichoic Acid Is Strongly Attenuated by Lipopolysaccharide-binding Protein

Sepsis and Pathophysiology of Anthrax in a Nonhuman Primate Model

Endogenous cortisol determines the circadian rhythm of lipopolysaccharide‐ but not lipoteichoic acid‐inducible cytokine release

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